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OBJECTIVES:. Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults. DESIGN:. Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study. SETTING:. Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021. PATIENTS/SUBJECTS:. Patients younger than 25 years receiving CRRT for acute kidney injury and/or fluid overload and requiring vasopressors. Patients receiving vasopressin were compared with patients receiving only norepinephrine/epinephrine. The impact of timing of vasopressin relative to CRRT start was assessed by categorizing patients as: early (on or before day 0), intermediate (days 1–2), and late (days 3–7). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 1016 patients, 665 (65%) required vasopressors in the first week of CRRT. Of 665, 248 (37%) received vasopressin, 473 (71%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (death, renal replacement therapy dependence, and/or > 125% increase in serum creatinine from baseline 90 days from CRRT initiation), and 195 (29%) liberated from CRRT on the first attempt within 28 days. Receipt of vasopressin was associated with higher odds of MAKE-90 (adjusted odds ratio [aOR], 1.80; 95% CI, 1.20–2.71; p = 0.005) but not liberation success. In the vasopressin group, intermediate/late initiation was associated with higher odds of MAKE-90 (aOR, 2.67; 95% CI, 1.17–6.11; p = 0.02) compared with early initiation. CONCLUSIONS:. Nearly two-thirds of children and young adults receiving CRRT required vasopressors, including over one-third who received vasopressin. Receipt of vasopressin was associated with more MAKE-90, although earlier initiation in those who received it appears beneficial. Prospective studies are needed to understand the appropriate timing, dose, and subpopulation for use of vasopressin.

Background: Although substantial motion at the acromioclavicular joint (ACJ) occurs during overhead shoulder motion, the influence of ACJ arthritis on postoperative outcomes of patients undergoing reverse total shoulder arthroplasty (rTSA) is unclear. We assessed the influence of ACJ arthritis, defined by degenerative radiographic changes, and its severity on clinical outcomes after primary rTSA. Methods: We conducted a retrospective review of a prospectively collected shoulder arthroplasty database of patients that underwent primary rTSA with a minimum 2-year clinical follow-up. Imaging studies of included patients were evaluated to assess ACJ arthritis classified by radiographic degenerative changes of the ACJ; severity was based upon size and location of osteophytes. Both the Petersson classification and the King classification (a modified Petersson classification addressing superior osteophytes and size of the largest osteophyte) were used to evaluate the severity of degenerative ACJ radiographic changes. Severe ACJ arthritis was characterized by large osteophytes (≥2 mm). Active range of motion (ROM) in abduction, forward elevation, and external and internal rotation as well as clinical outcome scores (American Shoulder and Elbow Surgeons Shoulder, Constant, Shoulder Pain and Disability Index, simple shoulder test, University of California, Los Angeles scores) were assessed both preoperatively and at the latest follow-up; outcomes were compared based on severity of ACJ arthritis. Multivariable linear regression models were used to determine whether increasing severity of ACJ arthritis was associated with poorer outcomes. Results: A total of 341 patients were included with a mean age of 71 ± 8 years and 55% were female. The mean follow-up was 5.1 ± 2.4 years. Preoperatively, there were no differences in outcomes based on the severity of ACJ pathology. Postoperatively, there were no differences in outcomes based upon the severity of ACJ arthritis except for greater preoperative to postoperative improvement in active internal rotation in patients with normal or grade 1 ACJ arthritis vs. grade 2 and 3 (3 ± 2 vs. 1 ± 2 and 1 ± 3, P = .029). Patients with ACJ arthritis and osteophytes ≥2 mm had less favorable Shoulder Pain and Disability Index scores, corresponding to greater pain (−49.3 ± 21.5 vs. −41.3 ± 26.8, P = .015). On multivariable linear regression, increased severity of ACJ arthritis was not independently associated with poorer postoperative ROM or outcome scores. Conclusion: Overall, our results demonstrate that greater ACJ arthritis severity score is not associated with poorer outcome scores and has minimal effect on ROM. However, patients with the largest osteophytes (≥2 mm) did have slightly worse pain postoperatively. Radiographic presence of high-stage ACJ arthritis should not alter the decision to undergo rTSA.

Different species of adenoviruses (AdVs) infect humans and animals and are known for their role as pathogens, especially in humans, with animals, primarily rodents, often serving as model systems. However, although we know over 100 types of human AdVs, we know comparatively little about the diversity of animal AdVs. Due to the fact that rodents are the most diverse family of mammals and a standard model system for human disease, we set out to sample African rodents native to the Democratic Republic of the Congo and test them for AdV DNA using a semi-nested consensus PCR. A total of 775 animals were tested, and viral DNA was detected in four of them. The AdV DNA found belongs to three different AdVs, all being closely related to murine adenovirus 2 (MAdV-2). Considering the genetic differences of the amplicon were 9%, 11% and 19% from MAdV-2 and at least 10% from each other, they seem to belong to up to three different novel types within the Murine mastadenovirus B species. This evidence of genetic diversity highlights the opportunities to isolate and study additional AdVs that infect rodents as models for AdV biology and pathology.

Background:. The purpose of this study was to evaluate the influence of the volume and type of sport on the development of cam-type femoroacetabular impingement and acetabular dysplasia. Methods:. The Physical Activity Questionnaire for Adolescents (PAQ-A) was administered to Iowa Bone Development Study participants at the age of 17 years to identify those who had participated in at least 2 seasons of high school interscholastic sports. Based on relative peak strain and ground reaction forces, subjects were grouped as power sport athletes (basketball, cheerleading, football, gymnastics, soccer, and volleyball), non-power sport athletes (wrestling, baseball, cross-country or track and field, softball, or tennis), or non-athletes. Using anteroposterior views of the left hip formatted from dual x-ray absorptiometry (DXA) scans, the alpha angle, head-neck offset ratio (HNOR), and lateral center-edge angle (LCEA) were evaluated longitudinally at the ages of 17, 19, and 23 years. Logistic regression was used to evaluate the odds of hip cam morphology (alpha angle >55° and/or HNOR 0.05). There were no significant differences in the odds of cam morphology or acetabular dysplasia in non-power sport athletes compared with non-athletes (all p > 0.05). Higher physical activity levels were significantly associated with an increase in the alpha angle (beta and standard error, 0.77° ± 0.30°; p = 0.011) and a decrease in the HNOR (−0.003 ± 0.001; p = 0.003), but not the LCEA (−0.05 ± 0.15; p = 0.744). Conclusions:. A higher volume of physical activity and participation in sports with higher peak strain and ground reaction forces during the process of skeletal maturation may increase the risk of developing cam morphology during late adolescence. Level of Evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Category: Ethics Introduction/Purpose: The objective of our study was to analyze COI nondisclosure for US based research articles that were published to three prevalent orthopaedic journals from the beginning of 2014 to the end of 2016. Methods: All US-based research articles published to FAI, JBJS, and JOA from the beginning of 2014 to the end of 2016 were reviewed. COI disclosure sections were analyzed to determine if a disclosure was made for first and/or last authors. Authors disclosing any financial relationship involving employment, royalties/licensing, speaking, and consulting fees were recorded as having disclosed a potential COI. First and last authors were then searched for using CMS Open Payments search tool to determine if they had received any of the aforementioned payment types. To determine if a COI nondisclosure (disclosure discrepancy) was present, an author’s disclosure statement for a published article was compared to CMS Open Payments data from the year prior to publication of the article. We used CMS data from the year prior to a publication to account for the time it takes to construct a paper and have it published. Results: Across all journals and years, we obtained disclosure accuracy data for 3,465 total first and last authors publishing 1,770 research articles. Within this sample, 7.1% (245/3,465) of the authors had a recorded undisclosed conflict-of-interest and 13.2% (233/1,770) of articles had a first and/or last author with an undisclosed potential conflict-of-interest. When looking at each journal individually over the three-year period, FAI contained the highest percentage of authors with undisclosed COI’s (42.3%), JBJS contained the lowest percent of authors with an undisclosed COI (4.6%), and JOA had an intermediate amount of authors with an undisclosed COI (7.0%). Conclusion: Discrepancies between payment disclosures made by authors and those published in the CMS database were present in all three journals reviewed in this study. The percentage of articles containing an author with a disclosure discrepancy varies widely between these journals. However, when analyzing the percentage of disclosure discrepancies by year, no trend was found.

During 2010-2011, we investigated interspecies transmission of partetraviruses between predators (humans and chimpanzees) and their prey (colobus monkeys) in Côte d'Ivoire. Despite widespread infection in all species investigated, no interspecies transmission could be detected by PCR and genome analysis. All sequences identified formed species- or subspecies (chimpanzee)-specific clusters, which supports a co-evolution hypothesis. [ABSTRACT FROM AUTHOR]

Objective: High-definition transcranial direct current stimulation (HD-tDCS) has the potential to improve cognitive functioning following neurological injury and in neurodegenerative conditions. In this case report, we present the first use of HD-tDCS in a person with severe anterograde amnesia following carbon monoxide poisoning., Method: The participant underwent two rounds of HD-tDCS that were separated by 3 months (Round 1 = 30 sessions; Round 2 = 31 sessions). We used finite element modeling of the participant's structural MRI to develop an individualized montage that targeted multiple brain regions involved in memory encoding, as identified by Neurosynth., Results: Overall, the participant's objective cognitive functioning improved significantly following Round 1, declined during the 2 months without HD-tDCS, and again improved following Round 2. Subjective informant reports from family and medical personnel followed this same pattern of improvement following each round with a decline in between rounds. We also provide preliminary evidence of altered brain activity during a learning/memory task using functional near-infrared spectroscopy, which may help establish the physiological effects of HD-tDCS in future work., Conclusion: Overall, these findings reinforce the potential value of HD-tDCS as a user-friendly method of enhancing cognition following anoxic/hypoxic brain injury.

Objective: The Digital Healthcare Act introduced the prescription of digital health applications under specific circumstances in 2019 in Germany. They are funded through the social security system. In market access of prescribed digital health applications, Germany is pioneering the market. There remains a gap in understanding the views of medical professionals on the incentives of using these applications. As prescription of digital health applications starts emerging in other European countries, we sought to generate an overview of incentives and barriers that affect the caregivers in their decision of promoting and prescribing them in Germany., Methods: A Rapid Review of the Web of Science database for the years 2017-2023 was performed using sensitive search strings. Two reviewers conducted a three-phase selection via title, abstract and full-text independently from each other. The quality of studies was assessed systematically by both reviewers. Both quantitative and qualitative studies with primary data were included, and study quality was assessed using a standardised form., Results: Out of 1643 initial results, 12 studies with information from 9302 physicians and psychotherapists were identified. Eight quantitative and four qualitative studies were included in the analysis. Key findings suggest that while between 40% and 60% of caregivers see relevant incentives mainly based on patients' benefits, 20-40% see relevant barriers. For the physicians' daily work, there were slightly more barriers than incentives identified in the quantitative synthesis. The qualitative studies revealed no relevant incentives that were not attributed to patients., Conclusion: While digital health solutions offer promising avenues for enhancing patient care, their acceptance among healthcare professionals hinges on addressing prevailing concerns. Continuous research and dialogues with the medical community are pivotal to harness the full potential of digital health applications in healthcare., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Although substantial motion at the acromioclavicular joint (ACJ) occurs during overhead shoulder motion, the influence of ACJ arthritis on postoperative outcomes of patients undergoing reverse total shoulder arthroplasty (rTSA) is unclear. We assessed the influence of ACJ arthritis, defined by degenerative radiographic changes, and its severity on clinical outcomes after primary rTSA., Methods: We conducted a retrospective review of a prospectively collected shoulder arthroplasty database of patients that underwent primary rTSA with a minimum 2-year clinical follow-up. Imaging studies of included patients were evaluated to assess ACJ arthritis classified by radiographic degenerative changes of the ACJ; severity was based upon size and location of osteophytes. Both the Petersson classification and the King classification (a modified Petersson classification addressing superior osteophytes and size of the largest osteophyte) were used to evaluate the severity of degenerative ACJ radiographic changes. Severe ACJ arthritis was characterized by large osteophytes (≥2 mm). Active range of motion (ROM) in abduction, forward elevation, and external and internal rotation as well as clinical outcome scores (American Shoulder and Elbow Surgeons Shoulder, Constant, Shoulder Pain and Disability Index, simple shoulder test, University of California, Los Angeles scores) were assessed both preoperatively and at the latest follow-up; outcomes were compared based on severity of ACJ arthritis. Multivariable linear regression models were used to determine whether increasing severity of ACJ arthritis was associated with poorer outcomes., Results: A total of 341 patients were included with a mean age of 71 ± 8 years and 55% were female. The mean follow-up was 5.1 ± 2.4 years. Preoperatively, there were no differences in outcomes based on the severity of ACJ pathology. Postoperatively, there were no differences in outcomes based upon the severity of ACJ arthritis except for greater preoperative to postoperative improvement in active internal rotation in patients with normal or grade 1 ACJ arthritis vs. grade 2 and 3 (3 ± 2 vs. 1 ± 2 and 1 ± 3, P  = .029). Patients with ACJ arthritis and osteophytes ≥2 mm had less favorable Shoulder Pain and Disability Index scores, corresponding to greater pain (-49.3 ± 21.5 vs. -41.3 ± 26.8, P  = .015). On multivariable linear regression, increased severity of ACJ arthritis was not independently associated with poorer postoperative ROM or outcome scores., Conclusion: Overall, our results demonstrate that greater ACJ arthritis severity score is not associated with poorer outcome scores and has minimal effect on ROM. However, patients with the largest osteophytes (≥2 mm) did have slightly worse pain postoperatively. Radiographic presence of high-stage ACJ arthritis should not alter the decision to undergo rTSA.

Background: Aeromedical evacuation provides critical care during long-distance transport of injured victims between medical facilities. Often, these victims sustain muscle trauma related to mechanical insults, such as crush. Understanding the effects of flight on injured muscle is important because the aircraft cabin represents an external environment with mild hypoxia-the cabin's altitude is 2,438 m instead of sea level. Because mild hypobaric hypoxia can alter gene expression in normal muscle and affect recovery patterns, it is beneficial to examine whether this type of hypoxia may also alter injury-related genes., Objective: The objective of this study was to verify the hypothesis that differential gene expression occurs in response to mild hypobaric hypoxia exposure in crush-injured muscle during two early recovery (preregeneration stage) time points., Methods: Twenty-four female mice were anesthetized, and the right gastrocnemius muscle underwent crush injury. Approximately 24 hours later, mice were exposed to normobaric normoxia or hypobaric hypoxia for 8-9 hours. After 32 or 48 hours of recovery, the mice were euthanized, and the right and left lateral gastrocnemius muscles were collected for microarray and bioinformatics analyses., Results: The study hypothesis was verified. There were 353 highly upregulated, differentially expressed genes identified in the injured muscle compared to the uninjured muscle. Mid1 was upregulated in both pressure conditions regardless of injury status. There were 52 and 15 differentially expressed genes at 32 and 48 hours postinjury, respectively, in the hypobaric hypoxia-exposed, injured muscle compared to the normobaric normoxia-exposed, injured muscle. The macrophage gene Cd68 correlated with other leukocyte-related genes., Discussion: These findings expand our understanding of the genetic changes that occur in muscle in response to a crush injury, including those related to the macrophage protein CD68. Nursing interventions addressing adequate functioning after crush muscle injury may need to consider the effects on Cd68 and its closely related genes. In addition, our results suggest a responsiveness of the gene Mid1 to flight-relevant hypobaric hypoxia. Changes in the expression of Mid1 may be appropriate in assessing the long-term health of flight crew members., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective  To evaluate a proposed three-dimensional (3D) printing process of a biomodel developed with the aid of fused deposition modeling (FDM) technology based on computed tomography (CT) scans of an individual with nonunion of a coronal femoral condyle fracture (Hoffa's fracture). Materials and Methods  Thus, we used CT scans, which enable the evaluation of the 3D volumetric reconstruction of the anatomical model, as well as of the architecture and bone geometry of sites with complex anatomy, such as the joints. In addition, it enables the development of the virtual surgical planning (VSP) in a computer-aided design (CAD) software. This technology makes it possible to print full-scale anatomical models that can be used in surgical simulations for training and in the choice of the best placement of the implant according to the VSP. In the radiographic evaluation of the osteosynthesis of the Hoffa's fracture nonunion, we assessed the position of the implant in the 3D-printed anatomical model and in the patient's knee. Results  The 3D-printed anatomical model showed geometric and morphological characteristics similar to those of the actual bone. The position of the implants in relation to the nonunion line and anatomical landmarks showed great accuracy in the comparison of the patient's knee with the 3D-printed anatomical model. Conclusion  The use of the virtual anatomical model and the 3D-printed anatomical model with the additive manufacturing (AM) technology proved to be effective and useful in planning and performing the surgical treatment of Hoffa's fracture nonunion. Thus, it showed great accuracy in the reproducibility of the virtual surgical planning and the 3D-printed anatomical model., Competing Interests: Conflito de Interesses Os autores não têm conflito de interesses a declarar., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background and Aim: Antibiotic-resistant Salmonella is a public health concern. Fluoroquinolones and extended-spectrum beta-lactams are widely used for the treatment of Salmonella infections. This study focused on the detection of plasmid-mediated quinolone resistance (PMQR) and extended-spectrum beta-lactamase (ESBL) genes among multidrug-resistant (MDR) Salmonella enterica isolated from broilers., Materials and Methods: A total of 40 non-typhoidal S. enterica isolates were collected from 28 broiler chicken farms in four Iraqi Governorates. These isolates were examined for their susceptibility to 10 antimicrobial agents by disk-diffusion method followed by polymerase chain reaction assay for the detection of PMQR determinants and ESBLs genes., Results: Salmonella strains revealed high levels of resistance to the following antibiotics: Nalidixic acid 100%, levofloxacin (LEV) 97.5%, amoxicillin-clavulanic acid 95.0%, tetracycline 92.5%, and nitrofurantoin 80.0%. Otherwise, all isolates were susceptible to cefotaxime and ceftriaxone. All isolates were MDR, with 15 different profiles observed. Among 38 amoxicillin/clavulanic acid-resistant Salmonella isolates, 20 (52.6%) had the bla TEM gene, while bla SHV, bla CTX-M, and bla OXA genes were not detected. Only 5 (12.8%) out of 39 LEV-resistant isolates were positive for qnrB , three of which had bla TEM. No qnrC or qnrD, qnrS , aac(6`)-Ib-cr , qunA , and oqxAB genes were found in any of the tested isolates., Conclusion: This study demonstrates that broiler chickens may be considered a potential source for spreading MDR non-typhoidal Salmonella and ESBL traits in poultry production. Therefore, it is important to continuously monitor ESBL and PMQR genes to avoid the spread of resistant strains in the food chain and impact public health., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Hassan, et al.)

Zoonotic spillover of animal viruses into human populations is a continuous and increasing public health risk. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the global impact of emergence. Considering the history and diversity of coronaviruses (CoVs), especially in bats, SARS-CoV-2 will likely not be the last to spillover from animals into human populations. We sampled and tested wildlife in the Central African country Cameroon to determine which CoVs are circulating and how they relate to previously detected human and animal CoVs. We collected animal and ecological data at sampling locations and used family-level consensus PCR combined with amplicon sequencing for virus detection. Between 2003 and 2018, samples were collected from 6,580 animals of several different orders. CoV RNA was detected in 175 bats, a civet, and a shrew. The CoV RNAs detected in the bats represented 17 different genetic clusters, coinciding with alpha ( n  = 8) and beta ( n  = 9) CoVs. Sequences resembling human CoV-229E (HCoV-229E) were found in 40 Hipposideridae bats. Phylogenetic analyses place the human-derived HCoV-229E isolates closest to those from camels in terms of the S and N genes but closest to isolates from bats for the envelope, membrane, and RNA-dependent RNA polymerase genes. The CoV RNA positivity rate in bats varied significantly (P < 0.001) between the wet (8.2 per cent) and dry seasons (4.5 per cent). Most sampled species accordingly had a wet season high and dry season low, while for some the opposite was found. Eight of the suspected CoV species of which we detected RNA appear to be entirely novel CoV species, which suggests that CoV diversity in African wildlife is still rather poorly understood. The detection of multiple different variants of HCoV-229E-like viruses supports the bat reservoir hypothesis for this virus, with the phylogenetic results casting some doubt on camels as an intermediate host. The findings also support the previously proposed influence of ecological factors on CoV circulation, indicating a high level of underlying complexity to the viral ecology. These results indicate the importance of investing in surveillance activities among wild animals to detect all potential threats as well as sentinel surveillance among exposed humans to determine emerging threats., (© The Author(s) 2021. Published by Oxford University Press.)

Enteroviruses infect humans and animals and can cause disease, and some may be transmitted across species barriers. We tested Central African wildlife and found Enterovirus RNA in primates (17) and rodents (2). Some sequences were very similar, while others were dissimilar to known species, highlighting the underexplored enterovirus diversity in wildlife.

Primary Objective: Identify the prevalence, characteristics, and psychological correlates of traumatic brain injury (TBI) among incarcerated individuals., Research Design: Three aims: (1) Determine the prevalence and characteristics of TBI in 1469 adults incarcerated in Wisconsin state prisons (1064 men, 405 women); (2) Characterize the relationship between mild TBI and mental illness in a sub-sample of men and women; (3) Reproduce the findings from Aim 1 and Aim 2 in an independent sample of 1015 adults incarcerated in New Mexico state prisons (600 men, 415 women)., Methods and Procedures: Standardized TBI assessment with structured clinical interviews and self-report questionnaires., Main Outcomes and Results: Rates of TBI were approximately five times greater than the general population, with a substantially higher rate of TBI caused by assault. In the Wisconsin sample, mild TBI was associated with greater levels of post-traumatic stress disorder (PTSD) among women (but not among men). In the New Mexico sample, TBI of any severity was associated with greater levels of major depressive disorder (MDD) among women (but not among men)., Conclusions: This study thus provides novel data on TBI and its correlates among individuals incarcerated in state prisons, and highlights a specific treatment need within the prison population.

Coronaviruses play an important role as pathogens of humans and animals, and the emergence of epidemics like SARS, MERS and COVID-19 is closely linked to zoonotic transmission events primarily from wild animals. Bats have been found to be an important source of coronaviruses with some of them having the potential to infect humans, with other animals serving as intermediate or alternate hosts or reservoirs. Host diversity may be an important contributor to viral diversity and thus the potential for zoonotic events. To date, limited research has been done in Africa on this topic, in particular in the Congo Basin despite frequent contact between humans and wildlife in this region. We sampled and, using consensus coronavirus PCR-primers, tested 3,561 wild animals for coronavirus RNA. The focus was on bats (38%), rodents (38%), and primates (23%) that posed an elevated risk for contact with people, and we found coronavirus RNA in 121 animals, of which all but two were bats. Depending on the taxonomic family, bats were significantly more likely to be coronavirus RNA-positive when sampled either in the wet (Pteropodidae and Rhinolophidae) or dry season (Hipposideridae, Miniopteridae, Molossidae, and Vespertilionidae). The detected RNA sequences correspond to 15 alpha- and 6 betacoronaviruses, with some of them being very similar (>95% nucleotide identities) to known coronaviruses and others being more unique and potentially representing novel viruses. In seven of the bats, we detected RNA most closely related to sequences of the human common cold coronaviruses 229E or NL63 (>80% nucleotide identities). The findings highlight the potential for coronavirus spillover, especially in regions with a high diversity of bats and close human contact, and reinforces the need for ongoing surveillance., Competing Interests: Metabiota (https://metabiota.com), Labyrinth Global Health (https://www.labyrinthgh.com), and Mosaic (https://mosaic.cm) are private contractors who receive funds from international donor organizations to conduct technical assistance and research. Metabiota employs or employed CK, FM, PMK, INL, FNK, JAL, PM, MM, UT, AG, BSS, DJM, JAA, CM, DOJ, KS, NDW, EMR, and CEL, Mosaic employs ML, and Labyrinth Global Health employs KS, MM and CEL. There are no patents, products in development or marketed products associated with this research to declare. The association with commercial entities that some of the authors have does not alter our adherence to PLOS ONE policies on sharing data and materials.

Adenoviruses (AdVs) are diverse pathogens of humans and animals, with several dozen bat AdVs already identified. Considering that over 100 human AdVs are known, and the huge diversity of bat species, many bat AdVs likely remain undiscovered. To learn more about AdV prevalence, diversity and evolution, we sampled and tested bats in Cameroon using several PCR assays for viral and host DNA. AdV DNA was detected in 14 % of the 671 sampled animals belonging to 37 different bat species. There was a correlation between species roosting in larger groups and AdV DNA detection. The detected AdV DNA belonged to between 28 and 44 different, mostly previously unknown, mastadenovirus species. The novel isolates are phylogenetically diverse and while some cluster with known viruses, others appear to form divergent new clusters. The phylogenetic tree of novel and previously known bat AdVs does not mirror that of the various host species, but does contain structures consistent with a degree of virus-host co-evolution. Given that closely related isolates were found in different host species, it seems likely that at least some bat AdVs have jumped species barriers, probably in the more recent past; however, the tree is also consistent with such events having taken place throughout bat AdV evolution. AdV diversity was highest in bat species roosting in large groups. The study significantly increased the diversity of AdVs known to be harboured by bats, and suggests that host behaviours, such as roosting size, may be what limits some AdVs to one species rather than an inability of AdVs to infect other related hosts.

Background/aims: Intrastromal corneal ring segments (ICRS) have been found to be useful in correcting keratoconus by decreasing irregular astigmatism, thereby potentially improving visual acuity. However, its long-term effects in keratoconus progression are not completely understood, mainly concerning the effects of age on ICRS implantation results. This study aimed to evaluate long-term effects of ICRS implantation according to age at implantation., Methods: We conducted a longitudinal retrospective study, where we evaluated patients with keratoconus who underwent ICRS implantation between 2004 and 2012., Results: We evaluated 34 eyes for 5 years post-operatively. The mean age of the 21 men and 7 women was 20.59 ± 4.65 years. Best spectacle-corrected visual acuity (BSCVA) improved from 0.32 ± 0.19 in the preoperative period to 0.46 ± 0.27 6 months post-operatively. After up to 5 years of follow-up, there was no significant difference in mean visual acuity of the group. As expected, there was a significant decrease in keratometric values after corneal ring implantation, which remained stable over the 5-year follow-up. Among the 34 cases analysed, nine (26%) showed signs of disease progression. In eight of the nine documented progression cases, patients were 21 years old or younger, revealing that these patients were sevenfold more likely to progress than those aged over 21 years., Conclusion: In our series of cases, ICRS implantation was shown to be an excellent treatment to reduce corneal curvature and improve visual acuity at all ages, but it did not stabilize the disease, especially in young patients with more aggressive forms of the keratoconus.

Different species of adenoviruses (AdVs) infect humans and animals and are known for their role as pathogens, especially in humans, with animals, primarily rodents, often serving as model systems. However, although we know over 100 types of human AdVs, we know comparatively little about the diversity of animal AdVs. Due to the fact that rodents are the most diverse family of mammals and a standard model system for human disease, we set out to sample African rodents native to the Democratic Republic of the Congo and test them for AdV DNA using a semi-nested consensus PCR. A total of 775 animals were tested, and viral DNA was detected in four of them. The AdV DNA found belongs to three different AdVs, all being closely related to murine adenovirus 2 (MAdV-2). Considering the genetic differences of the amplicon were 9%, 11% and 19% from MAdV-2 and at least 10% from each other, they seem to belong to up to three different novel types within the Murine mastadenovirus B species. This evidence of genetic diversity highlights the opportunities to isolate and study additional AdVs that infect rodents as models for AdV biology and pathology., (© 2019 The Authors.)

Rodent adenoviruses are important models for human disease. In contrast to the over 70 adenovirus types isolated from humans, few rodent adenoviruses are known, despite the vast diversity of rodent species. PCR and Sanger sequencing were used to investigate adenovirus diversity in wild rodents and shrews in Cameroon. Adenovirus DNA was detected in 13.8% of animals (n = 218). All detected sequences differ from known adenovirus types by more than 10% at the amino acid level, thus indicating up to 14 novel adenovirus species. These results highlight the diversity of rodent adenoviruses, their phylogeny, and opportunities for studying alternative adenovirus rodent models.

We applied metagenomic next-generation sequencing (mNGS) to detect Zaire Ebola virus (EBOV) and other potential pathogens from whole-blood samples from 70 patients with suspected Ebola hemorrhagic fever during a 2014 outbreak in Boende, Democratic Republic of the Congo (DRC) and correlated these findings with clinical symptoms. Twenty of 31 patients (64.5%) tested in Kinshasa, DRC, were EBOV positive by quantitative reverse transcriptase PCR (qRT-PCR). Despite partial degradation of sample RNA during shipping and handling, mNGS followed by EBOV-specific capture probe enrichment in a U.S. genomics laboratory identified EBOV reads in 22 of 70 samples (31.4%) versus in 21 of 70 (30.0%) EBOV-positive samples by repeat qRT-PCR (overall concordance = 87.1%). Reads from Plasmodium falciparum (malaria) were detected in 21 patients, of which at least 9 (42.9%) were coinfected with EBOV. Other positive viral detections included hepatitis B virus ( n  = 2), human pegivirus 1 ( n  = 2), Epstein-Barr virus ( n  = 9), and Orungo virus ( n  = 1), a virus in the Reoviridae family. The patient with Orungo virus infection presented with an acute febrile illness and died rapidly from massive hemorrhage and dehydration. Although the patient's blood sample was negative by EBOV qRT-PCR testing, identification of viral reads by mNGS confirmed the presence of EBOV coinfection. In total, 9 new EBOV genomes (3 complete genomes, and an additional 6 ≥50% complete) were assembled. Relaxed molecular clock phylogenetic analysis demonstrated a molecular evolutionary rate for the Boende strain 4 to 10× slower than that of other Ebola lineages. These results demonstrate the utility of mNGS in broad-based pathogen detection and outbreak surveillance., (Copyright © 2019 Li et al.)

In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

[This corrects the article DOI: 10.1371/journal.pone.0194647.].

We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. A risk factor/exposure survey was administered to individuals with high levels of exposure to wildlife. Serological testing was performed to evaluate prior infection with several wildlife viral pathogens. Follow up serology was performed on a subset of the cohort as well as close contacts of individuals. 1,312 individuals were enrolled in the study. Contact with a wide range of wildlife species was reported in both occupational and occasional contexts. The overall proportion of individuals seropositive to any of the tested wildlife pathogens was approximately 4.0%. However, persons employed as butchers demonstrated a seropositivity of 9.0% to at least one pathogen of interest. By contrast, individuals working as hunters had lower rates of seropositivity. Among the study population, a number of other behaviors showed correlation with seropositivity, including contact with particular wildlife species such as field rats. These results demonstrate the need to further explore zoonotic risks of particular activities regarding wildlife contact, and to better understand risks of persons working as butchers with wildlife species.

The increasing use of contact lenses worldwide has led to an increase in cases of Acanthamoeba keratitis, which are often associated with inappropriate cleaning of contact lenses and lens cases. This study aimed to retrospectively review 28 cases of Acanthamoeba keratitis in Porto Alegre (southern Brazil) and identify the risk factors and clinical outcomes of affected patients. Most patients had higher education (66.6%), all were users of contact lenses, mostly women (67.9%). Most patients were soft contact lens wearers (66.7%) and 85.7% used multipurpose cleaning solutions. Sixteen patients (64.0%) used to wear contact lenses while swimming and/or bathing. Pain was the most common symptom (92.6%). For treatment, patients used polyhexamethylene biguanide drops (92.6%), propamidine isethionate drops (81.5%), chlorhexidine drops (55.6%), topical corticosteroids (63.0%), and systemic corticosteroids (37.0%). Herpes simplex keratitis was the most common misdiagnosis (72.7%). The majority of patients (76.0%) underwent a corneal transplant to control the disease.

Introduction: Coxsackievirus B3 (CVB3) virus has been implicated as the causative agent of various outbreaks of clinical disease, including hand, foot, and mouth diseases, aseptic meningitis, acute myocarditis, and inflammatory cardiomyopathy., Methodology: Two hundred and nine undiagnosed cryopreserved specimens obtained from factory workers in Bandung, Indonesia, who displayed symptoms of acute febrile illness were gathered. Total RNA was isolated from serum and tested by conventional polymerase chain reaction (PCR) using Enterovirus genus-level primers and confirmed by sequencing. Concurrently, the virus was isolated in LLC-MK2 cells., Results: CVB3 virus was identified in an archived specimen from a patient who presented with symptoms of fever, headache, myalgia, and nausea. Sequencing results of the VP1 region from both the clinical sample and tissue culture supernatant showed 97% homology to a CVB3 virus isolate from Taiwan. Virus propagation in LLC-MK2 cell culture exhibited severe cytopathic effects two days post-inoculation., Conclusions: We report the first case of CVB3 from an undifferentiated febrile illness specimen from Indonesia.

Due to their ability to suppress a large part of the electron current and thus measuring directly the plasma potential, ion sensitive probes have begun to be widely tested and used in fusion devices. For these probes to work, almost perfect alignment with the total magnetic field is necessary. This condition cannot always be fulfilled due to the curvature of magnetic fields, complex magnetic structure, or magnetic field reconnection. In this perspective, we have developed a plasma potential probe (named Bunker probe) based on the principle of the ion sensitive probe but almost insensitive to its orientation with the total magnetic field. Therefore it can be used to measure the plasma potential inside fusion devices, especially in regions with complex magnetic field topology. Experimental results are presented and compared with Ball-Pen probe measurements taken under identical conditions. We have observed that the floating potential of the Bunker probe is indeed little affected by its orientation with the magnetic field for angles ranging from 90° to 30°, in contrast to the Ball-Pen probe whose floating potential decreases towards that of a Langmuir probe if not properly aligned with the magnetic field.

The family Arteriviridae presently includes a single genus Arterivirus. This genus includes four species as the taxonomic homes for equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), porcine respiratory and reproductive syndrome virus (PRRSV), and simian hemorrhagic fever virus (SHFV), respectively. A revision of this classification is urgently needed to accommodate the recent description of eleven highly divergent simian arteriviruses in diverse African nonhuman primates, one novel arterivirus in an African forest giant pouched rat, and a novel arterivirus in common brushtails in New Zealand. In addition, the current arterivirus nomenclature is not in accordance with the most recent version of the International Code of Virus Classification and Nomenclature. Here we outline an updated, amended, and improved arterivirus taxonomy based on current data. Taxon-specific sequence cut-offs are established relying on a newly established open reading frame 1b phylogeny and pairwise sequence comparison (PASC) of coding-complete arterivirus genomes. As a result, the current genus Arterivirus is replaced by five genera: Equartevirus (for EAV), Rodartevirus (LDV + PRRSV), Simartevirus (SHFV + simian arteriviruses), Nesartevirus (for the arterivirus from forest giant pouched rats), and Dipartevirus (common brushtail arterivirus). The current species Porcine reproductive and respiratory syndrome virus is divided into two species to accommodate the clear divergence of the European and American "types" of PRRSV, both of which now receive virus status. The current species Simian hemorrhagic fever virus is divided into nine species to accommodate the twelve known simian arteriviruses. Non-Latinized binomial species names are introduced to replace all current species names to clearly differentiate them from virus names, which remain largely unchanged.

Objectives: Considering the evident relationship between periodontitis and cardiovascular diseases in humans, we aimed to study the in vitro vascular reactivity of aorta rings prepared from rats with ligature-induced periodontitis., Methods: Seven days after the induction of unilateral periodontitis, the animals were euthanised; rings were prepared from the descending abdominal aortas and mounted in tissue baths for the in vitro measurement of the isometric force responses to norepinephrine (NE) and acetylcholine (ACh), as well as in the presence of inhibitors of nitric oxide synthase (NOS) and cycloxygenase (COX) isoenzymes. Aortic COX and NOS gene expressions were analysed by RT-PCR, as well as protein COX-2 expression by Western blot., Results: Periodontitis resulted in significant alveolar bone loss and did not affect arterial pressure. However, both NE-induced contraction and ACh-induced relaxation were significantly decreased and related to the presence of endothelium. Diminished eNOS and augmented COX-2 and iNOS expressions were found in the aortas from rats with periodontitis, and the pharmacological inhibition of COX-2 or iNOS improved the observed vasomotor deficiencies., Conclusions: We can thus conclude that periodontitis induces significant endothelial dysfunction in rat aorta which is characterized by decreased eNOS expression and mediated by upregulated iNOS and COX-2 products., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We report unbiased metagenomic detection of chikungunya virus (CHIKV), Ebola virus (EBOV), and hepatitis C virus (HCV) from four human blood samples by MinION nanopore sequencing coupled to a newly developed, web-based pipeline for real-time bioinformatics analysis on a computational server or laptop (MetaPORE). At titers ranging from 10(7)-10(8) copies per milliliter, reads to EBOV from two patients with acute hemorrhagic fever and CHIKV from an asymptomatic blood donor were detected within 4 to 10 min of data acquisition, while lower titer HCV virus (1 × 10(5) copies per milliliter) was detected within 40 min. Analysis of mapped nanopore reads alone, despite an average individual error rate of 24 % (range 8-49 %), permitted identification of the correct viral strain in all four isolates, and 90 % of the genome of CHIKV was recovered with 97-99 % accuracy. Using nanopore sequencing, metagenomic detection of viral pathogens directly from clinical samples was performed within an unprecedented <6 hr sample-to-answer turnaround time, and in a timeframe amenable to actionable clinical and public health diagnostics.

Enteroviruses, members of the Picornaviridae family, are ubiquitous viruses responsible for mild to severe infections in human populations around the world. In 2010 Pointe-Noire, Republic of Congo recorded an outbreak of acute flaccid paralysis (AFP) in the humans, caused by wild poliovirus type 1 (WPV1). One month later, in the Tchimpounga sanctuary near Pointe-Noire, a chimpanzee developed signs similar to AFP, with paralysis of the lower limbs. In the present work, we sought to identify the pathogen, including viral and bacterial agents, responsible for this illness. In order to identify the causative agent, we evaluated a fecal specimen by PCR and sequencing. A Human enterovirus C, specifically of the EV-C99 type was potentially responsible for the illness in this chimpanzee. To rule out other possible causative agents, we also investigated the bacteriome and the virome using next generation sequencing. The majority of bacterial reads obtained belonged to commensal bacteria (95%), and the mammalian virus reads matched mainly with viruses of the Picornaviridae family (99%), in which enteroviruses were the most abundant (99.6%). This study thus reports the first identification of a chimpanzee presenting AFP most likely caused by an enterovirus and demonstrates once again the cross-species transmission of a human pathogen to an ape.

Background: A new Marseilleviridae virus family member, giant blood Marseille-like (GBM) virus, was recently reported in persons from France in the serum of an infant with adenitis, in the blood of 4% of healthy blood donors, and in 9% of multiply transfused thalassemia patients. These results suggested the presence of a nucleocytoplasmic large DNA virus potentially transmissible by blood product transfusion., Study Design and Methods: To investigate this possibility we tested the plasma from 113 US blood donors and 74 multiply transfused Cameroon patients for GBM viral DNA using highly sensitive polymerase chain reaction (PCR) assays., Results: GBM DNA was not detected by nested PCR in any of these 187 human specimens., Conclusions: Further testing is required to confirm the occurrence of human GBM virus infections., (© 2015 AABB.)

Innate pro-inflammatory processes, such as chemokine signaling and leukocyte infiltration, predominate during the first 48 h after an acute skeletal muscle injury. However, the time course of chemokine expression and its relationship to leukocyte infiltration after acute muscle injury within this early post-injury time period has not been investigated. In this study, 46 anesthetized female C57BL/6NHsd mice underwent a closed crush injury of the gastrocnemius muscle and were euthanized 4, 8, 24 and 48 h post-injury. Microarray analysis found 14 chemokine genes to be up-regulated during this period, 12 of which are involved in macrophage or neutrophil chemotaxis, with up-regulation peaking at either 8 or 48 h. RT-PCR analysis on select chemokines confirmed the microarray activation pattern. Neutrophil infiltration patterns mirrored the time course of neutrophil-related chemokines with Gr-1-, 1A8- and 7/4-positive neutrophils infiltrating the muscle 4 h after injury, decreasing at 48 h. Conversely, gene expression and relative quantification levels of macrophage-related chemokines Ccl2 and Ccl7 peaked at 8 h, preceding the infiltration of CD68- and F4/80-positive macrophages, and protein expression of Ccl2 in the muscle. The up-regulation of other macrophage-related chemokines and their receptors peaked at 48 h post-injury., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: In experimental periodontitis, non-steroidal antiinflammatory drugs (NSAIDs) effectively inhibit the resultant alveolar bone loss. However, their deleterious gastric effects, observed in both animals and humans, dramatically limit their long-term use. It has been proven that the addition of a hydrogen sulfide (H2S)-releasing moiety to classical NSAID structures results in antiinflammatory compounds with improved gastric safeness. In this way, we decided to compare the effects of naproxen with its H2S-releasing derivative ATB-346 on ligature-induced periodontitis in rats., Methods: Male Holtzman rats had a cotton ligature placed subgingivally around the lower right first molar during 7 days. During this period, groups of animals were daily treated with Na2S (a spontaneous H2S donor) or equimolar oral doses of naproxen (10 mg/kg) or ATB-346 (16 mg/kg). The mandibles were finally collected for histological analysis, radiographical measurements of alveolar bone loss and micro-computed tomography (μCT) analysis. Interleukin (IL)-1β, IL-6 and IL-10 were quantified in gingiva samples, and the stomachs were also collected for scoring of tissue damage and measurement of myeloperoxidase (MPO, a marker of granulocyte infiltration)., Results: Ligature-induced bone loss was significantly inhibited by all the treatments, although only ATB-346 treatment resulted in significant inhibition of bone defect and other histological characteristics (such as flatness of the gingival epithelium, chronic inflammatory cell infiltration and loss of connective tissue in the gingival papillae). Both naproxen and ATB-346 inhibited the increase of gingival IL-1β and IL-6 secondary to periodontitis, but IL-10 was unaffected. Significant damage and increased MPO contents were only found in the stomachs of the naproxen-treated animals., Conclusion: The H2S-releasing moiety in the ATB-346 compound not only does not impair the effects of the parent naproxen on periodontitis, but also improves bone quality and prevents the gastric mucosa damage due to prostaglandin inhibition, thus configuring a potentially new adjuvant therapy for periodontal diseases.

Lymphocytic choriomeningitis virus (LCMV) can cause acute fatal disease on all continents but was never detected in Africa. We report the first detection of LCMV RNA in a common European house mouse (Mus musculus domesticus) in Africa. Phylogenetic analyses show a close relationship with North American strains. These findings suggest that there is a risk of the appearance of LCMV acute encephalitis cases. This is a perfect example of virus dissemination by its natural host that may have dramatic public health consequences., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Zoonotic transmission of lethal henipaviruses (HNVs) from their natural fruit bat reservoirs to humans has only been reported in Australia and South/Southeast Asia. However, a recent study discovered numerous HNV clades in African bat samples. To determine the potential for HNV spillover events among humans in Africa, here we examine well-curated sets of bat (Eidolon helvum, n = 44) and human (n = 497) serum samples from Cameroon for Nipah virus (NiV) cross-neutralizing antibodies (NiV-X-Nabs). Using a vesicular stomatitis virus (VSV)-based pseudoparticle seroneutralization assay, we detect NiV-X-Nabs in 48% and 3-4% of the bat and human samples, respectively. Seropositive human samples are found almost exclusively in individuals who reported butchering bats for bushmeat. Seropositive human sera also neutralize Hendra virus and Gh-M74a (an African HNV) pseudoparticles, as well as live NiV. Butchering bat meat and living in areas undergoing deforestation are the most significant risk factors associated with seropositivity. Evidence for HNV spillover events warrants increased surveillance efforts.

Background: Unintentional injury or trauma remains the leading cause of death among young adults. About one fifth of these trauma patients require care in an intensive care unit (ICU) because of severity of injuries and comorbidities. Patients hospitalized in an ICU are at increased risk for nosocomial infections, such as urinary tract infections, pneumonia, bacteremia, and wound infections. Many of these patients will develop sepsis or septic shock, and some will progress to multiple organ failure and death. The balance between the proinflammatory and counterinflammatory immune response appears to be a driving factor in this progression. At present, there is no proposed method for the timely detection of the immune status in trauma patients, making rational decisions to use immune-altering therapies difficult., Objective: We demonstrate that flow cytometry, with its capabilities to characterize and/or enumerate (a) leukocyte subtypes, (b) leukocyte activation markers, (c) leukocyte-derived cytokines and microvesicles, and (d) leukocyte function is well suited to monitor the immune status of critically ill trauma patients., Methods: Information for the review was obtained from the extant literature., Discussion: We suggest that flow cytometry is a research method that might aid nurse scientists in investigating the immune status of critically ill patients, the recovery status of conditions such as hemorrhagic shock and tissue injury and the relationship between cancer disease progression and symptoms. Therefore, flow cytometry has the potential to broaden nursing research priority areas so that a comprehensive approach to understanding the cellular response is attained.

HCV genotype 4 is prevalent in many African countries, yet little is known about the genotype׳s epidemic history on the continent. We present a comprehensive study of the molecular epidemiology of genotype 4. To address the deficit of data from the Democratic Republic of the Congo (DRC) we PCR amplified 60 new HCV isolates from the DRC, resulting in 33 core- and 48 NS5B-region sequences. Our data, together with genotype 4 database sequences, were analysed using Bayesian phylogenetic approaches. We find three well-supported intra-genotypic lineages and estimate that the genotype 4 common ancestor existed around 1733 (1650-1805). We show that genotype 4 originated in central Africa and that multiple lineages have been exported to north Africa since ~1850, including subtype 4a which dominates the epidemic in Egypt. We speculate on the causes of the historical intra-continental spread of genotype 4, including population movements during World War 2., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)