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Abstract Intracortical brain-computer interfaces (iBCIs) enable people with tetraplegia to gain intuitive cursor control from movement intentions. To translate to practical use, iBCIs should provide reliable performance for extended periods of time. However, performance begins to degrade as the relationship between kinematic intention and recorded neural activity shifts compared to when the decoder was initially trained. In addition to developing decoders to better handle long-term instability, identifying when to recalibrate will also optimize performance. We propose a method, “MINDFUL”, to measure instabilities in neural data for useful long-term iBCI, without needing labels of user intentions. Longitudinal data were analyzed from two BrainGate2 participants with tetraplegia as they used fixed decoders to control a computer cursor spanning 142 days and 28 days, respectively. We demonstrate a measure of instability that correlates with changes in closed-loop cursor performance solely based on the recorded neural activity (Pearson r = 0.93 and 0.72, respectively). This result suggests a strategy to infer online iBCI performance from neural data alone and to determine when recalibration should take place for practical long-term use.

Abstract Introduction This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT). Methods Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy’s Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified. Results 95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT. Conclusion This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results. Clinical significance The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL). Research question What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients? Aim To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy. Null hypothesis There is no association between salivary proteins and onset/severity of OM in HNC patients.

Efficient cattle production and provision of animal-sourced foods in much of Africa is constrained by vector-borne bacterial and protozoal diseases. Effective vaccines are not currently available for most of these infections resulting in a continuous disease burden that limits genetic improvement. We tested whether stimulation of innate immunity using the Toll-like Receptor (TLR) 7 agonist imiquimod, formulated with saponin and water-in-oil emulsion, would protect against morbidity and mortality due to Anaplasma marginale, a tick-borne pathogen of cattle highly endemic in west Africa. In Trial 1, haplotype matched Friesian x Sanga (F1) A. marginale negative calves were allocated to either the experimental group (n = 10) and injected with the synthetic TLR 7 agonist/saponin formulation or to an untreated control group (n = 10). TLR7 agonist/saponin injected calves responded with significantly elevated rectal temperature, enlarged regional lymph nodes, and elevated levels of IL-6 post-injection as compared to control group calves. All calves were then allowed to graze in pasture for natural exposure to tick transmission. All calves in both groups acquired A. marginale, consistent with the high transmission rate in the endemic region. The need for antibiotic treatment, using pre-existing criteria, was significantly lower in the experimental group (odds ratio for not requiring treatment was 9.3, p = 0.03) as compared to the control group. Despite treatment, 6/10 calves in the control group died, reflecting treatment failures that are typical of anaplasmosis in the acute phase, while mortality in the experimental group was 1/10 (odds ratio for survival was 13.5, p = 0.03). The trial was then repeated using 45 Friesian x Sanga calves per group. In Trial 2, the odds ratios for preventing the need for treatment and for mortality in the TLR7 agonist/saponin experimental group versus the control group were 5.6 (p = 0.0002) and 7.0 (p = 0.004), respectively, reproducing the findings of the initial trial. Together these findings demonstrate that innate immune stimulation using a TLR7 agonist formulated with saponin and water-in-oil emulsion provides significant protection against disease caused by tick borne A. marginale in highly susceptible cross-bred cattle, critically important for their potential to increase productivity for smallholder farmers in Africa.

Abstract Background Dental erosion is a disease of the oral cavity where acids cause a loss of tooth enamel and is defined as having no bacterial involvement. The tooth surface is protected from acid attack by salivary proteins that make up the acquired enamel pellicle (AEP). Bacteria have been shown to readily degrade salivary proteins, and some of which are present in the AEP. This study aimed to explore the role of bacteria in dental erosion using a multi-omics approach by comparing saliva collected from participants with dental erosion and healthy controls. Results Salivary proteomics was assessed by liquid-chromatography mass spectrometry (LC–MS) and demonstrated two altered AEP proteins in erosion, prolactin inducible protein (PIP), and zinc-alpha-2 glycoprotein (ZAG). Immunoblotting further suggested that degradation of PIP and ZAG is associated with erosion. Salivary microbiome analysis was performed by sequencing the bacterial 16S rRNA gene (V1-V2 region, Illumina) and showed that participants with dental erosion had a significantly (p

Abstract Orthodontic tooth movement (OTM) occurs through proteolytic remodelling within the periodontium following the application of external force to the tooth. This study describes the first characterization of the salivary peptidome and protease profile during the alignment stage of fixed appliance orthodontic treatment. Unstimulated whole mouth saliva from 16 orthodontic patients (10 males, 6 females, mean (SD) age 15.2 (1.6) years) was collected prior to fixed appliance placement (T1), 1-h (T2), 1-week (T3) following fixed appliance placement and on completion of mandibular arch alignment (T4). Salivary peptides were extracted using filtration followed by mass spectrometry to identify amino acid sequences. Protease prediction was carried out in silico using Proteasix and validated with gelatin zymography and enzyme-linked immunosorbent assay. A total of 2852 naturally-occurring peptides were detected, originating from 436 different proteins. Both collagen and statherin-derived peptide levels were increased at T2. Proteasix predicted 73 proteases potentially involved in generating these peptides, including metalloproteinases, calpains and cathepsins. Changes in predicted activity of proteases over time were also observed, with most metalloproteinases showing increased predicted activity at T2–T3. Increased gelatinolytic activity and MMP8/MMP9 levels were detected at T3. Collectively, multiple protein targets and changes in protease-predicted activity during OTM have been identified.

Abstract We estimated the prevalence of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), carbapenem-resistant Enterobacterales (CRE), and methicillin-resistant Staphylococcus aureus (MRSA) in communities and hospitals in Kenya to identify human colonization with multidrug-resistant bacteria. Nasal and fecal specimen were collected from inpatients and community residents in Nairobi (urban) and Siaya (rural) counties. Swabs were plated on chromogenic agar to presumptively identify ESCrE, CRE and MRSA isolates. Confirmatory identification and antibiotic susceptibility testing were done using the VITEK®2 instrument. A total of 1999 community residents and 1023 inpatients were enrolled between January 2019 and March 2020. ESCrE colonization was higher in urban than rural communities (52 vs. 45%; P = 0.013) and in urban than rural hospitals (70 vs. 63%; P = 0.032). Overall, ESCrE colonization was ~ 18% higher in hospitals than in corresponding communities. CRE colonization was higher in hospital than community settings (rural: 7 vs. 1%; urban: 17 vs. 1%; with non-overlapping 95% confidence intervals), while MRSA was rarely detected (≤ 3% overall). Human colonization with ESCrE and CRE was common, particularly in hospitals and urban settings. MRSA colonization was uncommon. Evaluation of risk factors and genetic mechanisms of resistance can guide prevention and control efforts tailored to different environments.

The thermal characteristics of a typha-starch composite have been determined in this study in order to improve thermal comfort of the buildings in tropical environments. From six samples of this mixture of granulometry (0.425 mm; 1.25 mm and 1.70 mm), the kinetics of the water desorption have been characterized and the thermal properties of these materials were also studied. The results obtained indicate that the samples have a high rate of water desorption recorded in the first ten and fifteen days with proportions in loss of water which vary from 7% to 18.75%. The thermal conductivity obtained for samples without a binder (starch) varies from 0.1046 W.m−1K−1 to 0.1242 W.m−1K−1 and from 0.094 W.m−1K−1 to 0.5345 W.m−1K−1 for the composites. The thermal diffusivity evolves between 9.010−8 m².s−1 and 3.77.10−7m².s−1. In view of these results and according to the American National Standards Institute (ANSI 208, 1999), all the samples prepared except the formulation (0.425 mm + 20% starch) have good thermal properties for improving thermal comfort of buildings and the composite fraction (typha 1.70 mm + 20% starch) seems to be the optimal composition. The latter could be recommended as a local available insulation material to be integrated into the buildings in tropical environments in the form of sub-ceiling, instead of the widely used Isorel insulation panels (k = 0.82 W.m−1K−1) and plywood panels (k = 1.08 W.m−1K−1) of higher thermal conductivities and cost. For the first time in Africa, such a combination of local materials (Typha-amidon) used to improve energy efficiency has been demonstrated on the roof of the building envelope. The resulting scientific advances are linked to the originality of the formulation and the proportions of each material used to obtain the best composite. The development impacts of its implementation are directly linked to Sustainable Development Goals 1, 2, 7, 8, 14 and 15 (SDGs), as well as the African Union's Agenda 2063.

Hospitals can be overburdened with large numbers of patients with severe infectious conditions during infectious disease outbreaks. Such outbreaks or epidemics put tremendous pressure on the admission capacity of care facilities in the concerned region, negatively affecting the elective program within these facilities. Such situations have been observed during the recent waves of the coronavirus disease pandemic. Owing to the imminent threat of a “tripledemic” by new variants of the coronavirus disease (such as the new Omicron XBB.1.16 strain), influenza, and respiratory syncytial virus during future winter seasons, healthcare agencies should take decisive steps to safeguard hospitals' surge capacity while continuing to provide optimal and safe care to a potentially large number of patients in their trusted home environment. Preparedness of health systems for infectious diseases will require dynamic interaction between a continuous assessment of region-wide available hospital capacity and programs for intensive home treatment of patients who can spread the disease. In this viewpoint, we describe an innovative, dynamic coupling system between hospital surge capacity and cascading activation of a nationwide system for remote patient monitoring. This approach was developed using the multi-criteria decision analysis methodology, considering previously published real-life experiences on remote patient monitoring.

The outcome of bacterial infection management relies on prompt diagnosis and effective treatment, but conventional antimicrobial susceptibility testing can be slow and labor-intensive. Therefore, this study aims to predict phenotypic antimicrobial susceptibility of selected beta-lactam antimicrobials in the bacteria of the family Enterobacteriaceae from different beta-lactamase resistance genotypes. Using human datasets extracted from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program conducted by Pfizer and retail meat datasets from the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS), we used a robust or weighted least square multivariable linear regression modeling framework to explore the relationship between antimicrobial susceptibility data of beta-lactam antimicrobials and different types of beta-lactamase resistance genes. In humans, in the presence of the blaCTX-M-1, blaCTX-M-2, blaCTX-M-8/25, and blaCTX-M-9 groups, MICs of cephalosporins significantly increased by values between 0.34–3.07 μg/mL, however, the MICs of carbapenem significantly decreased by values between 0.81–0.87 μg/mL. In the presence of carbapenemase genes (blaKPC, blaNDM, blaIMP, and blaVIM), the MICs of cephalosporin antimicrobials significantly increased by values between 1.06–5.77 μg/mL, while the MICs of carbapenem antimicrobials significantly increased by values between 5.39–67.38 μg/mL. In retail meat, MIC of ceftriaxone increased significantly in the presence of blaCMY-2, blaCTX-M-1, blaCTX-M-55, blaCTX-M-65, and blaSHV-2 by 55.16 μg/mL, 222.70 μg/mL, 250.81 μg/mL, 204.89 μg/mL, and 31.51 μg/mL respectively. MIC of cefoxitin increased significantly in the presence of blaCTX-M-65 and blaTEM-1 by 1.57 μg/mL and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of cefoxitin increased by an average of 8.66 μg/mL over 17 years. Compared to E. coli isolates, MIC of cefoxitin in Salmonella enterica isolates decreased significantly by 0.67 μg/mL. On the other hand, MIC of ceftiofur increased in the presence of blaCTX-M-1, blaCTX-M-65, blaSHV-2, and blaTEM-1 by 8.82 μg/mL, 9.11 μg/mL, 8.18 μg/mL, and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of ceftiofur increased by an average of 10.20 μg/mL over 14 years. The ability to predict antimicrobial susceptibility of beta-lactam antimicrobials directly from beta-lactamase resistance genes may help reduce the reliance on routine phenotypic testing with higher turnaround times in diagnostic, therapeutic, and surveillance of antimicrobial-resistant bacteria of the family Enterobacteriaceae.

Abstract Escherichia coli is a Gram-negative bacterium that colonises the human intestine and virulent strains can cause severe diarrhoeal and extraintestinal diseases. The protein SslE is secreted by a range of pathogenic and commensal E. coli strains. It can degrade mucins in the intestine, promotes biofilm maturation and it is a major determinant of infection in virulent strains, although how it carries out these functions is not well understood. Here, we examine SslE from the commensal E. coli Waksman and BL21 (DE3) strains and the enterotoxigenic H10407 and enteropathogenic E2348/69 strains. We reveal that SslE has a unique and dynamic structure in solution and in response to acidification within mature biofilms it can form a unique aggregate with amyloid-like properties. Furthermore, we show that both SslE monomers and aggregates bind DNA in vitro and co-localise with extracellular DNA (eDNA) in mature biofilms, and SslE aggregates may also associate with cellulose under certain conditions. Our results suggest that interactions between SslE and eDNA are important for biofilm maturation in many E. coli strains and SslE may also be a factor that drives biofilm formation in other SslE-secreting bacteria.

Background. A qualitative evaluation study of the prematurely terminated PrEgabalin Lidocaine Capsaicin Neuropathic Pain (PELICAN) study was performed. The PELICAN study aimed to examine pain management for localized neuropathic pain (LNP), as epidemiological figures have shown a high percentage of LNP patients in Belgium. The study compared systemic and topical medications according to pain relief, adverse effects, and several measures of quality of life. Objective. Achieving better study patient recruitment through qualitative research. To investigate and determine the causes of the observed recruitment problems in the PELICAN study, pain centers involved in the study as well as nonrecruiting pain centers were included. Furthermore, it aimed to highlight the positive and negative lessons learned from the conducted study and the number of obstacles the team had to overcome. Methods. A qualitative study, using a mixed methods approach, was performed. Multiple pain centers in Belgium completed an online survey, after which a structured interview was conducted to elaborate the responses in more detail. The broad topics of these meetings were feedback about the study, reviewing survey answers, and actions undertaken to enhance recruitment. Results. Different factors contributed to the low recruitment rate in the PELICAN study, such as limited and late referral from the general practitioners to the Belgian pain centers, insufficient internal referrals from nonpain specialists, lack of specific expertise on LNP in some centers, scarcity of staff, limited reimbursement to administer complex analgesic schemes, overestimation of the patient population, and the reluctance of patients to participate in pain research. Additionally, shortcomings in the implemented study design and the need for more logistical investments were identified. Conclusion. The findings of the qualitative study demonstrate the need for further, more varied LNP research in Belgium, not limited to pharmacological studies. It also sheds important light on the recruitment obstacles that may be faced during these studies. Future studies could support this research by offering better proposals for feasibility and recruitment, for instance, by designing and conducting a compelling pilot study or applying social media during the recruitment phase. Clinical Trials. This trial is registered with NCT03348735. EUDRACT number 2018-003617-17.

Objective: Digital mammography can reveal not only breast cancer but also breast arterial calcification (BAC), which can indicate potential coronary artery disease. To explore ways to inform women of their BAC status in the context of a standard mammography results letter, we conducted a preliminary study comparing gain- and loss-framed messages to encourage follow-up cardiovascular care. Methods: U.S. women over age 40 with no heart disease history (N = 227) were randomly assigned to view a mammography letter including BAC information in one of seven ways (three gain-framed messages, three loss-framed messages, one comparison message). Results: Post-test measures indicated no significant differences on BAC knowledge, recall of test results and recommendations, perceived message effectiveness, or behavioral intentions for follow-up. Conclusion: Despite showing no significant differences between message conditions, results supported the messages' ability to clearly convey BAC information and encourage intention for follow-up cardiovascular care. Innovation: This experimental study represents the first published report examining the inclusion of BAC screening results within the mammography letter. It also explored the use of message framing in a dual detection–prevention context and suggests that future work should test the effects of including both framing tactics in messages designed to target dual-focus contexts.

Abstract Background The relationship between antibiotic use and antimicrobial resistance varies with cultural, socio-economic, and environmental factors. We examined these relationships in Kibera, an informal settlement in Nairobi—Kenya, characterized by high population density, high burden of respiratory disease and diarrhea. Methods Two-hundred households were enrolled in a 5-month longitudinal study. One adult (≥ 18 years) and one child (≤ 5 years) participated per household. Biweekly interviews (n = 1516) that included questions on water, sanitation, hygiene, and antibiotic use in the previous two weeks were conducted, and 2341 stool, 2843 hand swabs and 1490 drinking water samples collected. Presumptive E. coli (n = 34,042) were isolated and tested for susceptibility to nine antibiotics. Results Eighty percent of presumptive E. coli were resistant to ≥ 3 antibiotic classes. Stool isolates were resistant to trimethoprim (mean: 81%), sulfamethoxazole (80%), ampicillin (68%), streptomycin (60%) and tetracycline (55%). Ninety-seven households reported using an antibiotic in at least one visit over the study period for a total of 144 episodes and 190 antibiotic doses. Enrolled children had five times the number of episodes reported by enrolled adults (96 vs. 19). Multivariable linear mixed-effects models indicated that children eating soil from the household yard and the presence of informal hand-washing stations were associated with increased numbers of antimicrobial-resistant bacteria (counts increasing by 0·27–0·80 log10 and 0·22–0·51 log10 respectively, depending on the antibiotic tested). Rainy conditions were associated with reduced carriage of antimicrobial-resistant bacteria (1·19 to 3·26 log10 depending on the antibiotic tested). Conclusions Antibiotic use provided little explanatory power for the prevalence of antimicrobial resistance. Transmission of resistant bacteria in this setting through unsanitary living conditions likely overwhelms incremental changes in antibiotic use. Under such circumstances, sanitation, hygiene, and disease transmission are the limiting factors for reducing the prevalence of resistant bacteria.

Florida’s freshwater spring and river ecosystems have been deteriorating due to direct and indirect human impacts. However, while the conservation and restoration strategies employed to mitigate these effects often rely on faunal surveys that go back several decades, the local ecosystem shifts tend to have much deeper roots that predate those faunal surveys by centuries or millennia. Conservation paleobiology, an approach which enhances our understanding of the past states of ecosystems, allows for comparison of modern faunal communities with those prior to significant human impacts. This study examines the historical record of freshwater mollusk assemblages from two spring-fed river systems, the Wakulla and Silver/Ocklawaha Rivers. Specifically, we compared fossil assemblages (latest Pleistocene - early Holocene) and live mollusk assemblages in the two targeted river systems. Bulk sampling of the fossil record (20 sites; 70 samples; 16,314 specimens) documented relatively diverse mollusk assemblages that consist of a suite of native freshwater species that is similar across the studied systems. In contrast, sampling of live communities (24 sites; 138 samples; 7,572 specimens) revealed depauperate species assemblies characterized by the absence of multiple native freshwater species commonly found in fossil samples, the widespread presence of introduced species, and dominance of brackish-tolerant species at the lower Wakulla River sites. Unlike fossil mollusk assemblages, live mollusk assemblages differ notably between the two river systems due to differences in relative abundance of introduced species (Melanoides tuberculata and Corbicula fluminea) and the presence of brackish-tolerant mollusks in the coastally influenced Wakulla River. The diverse, exclusively freshwater mollusk associations comparable across multiple river systems documented in the fossil record provide a historical perspective on the past state of freshwater river ecosystems complementing data provided by modern surveys. The conservation paleobiology approach used in this study reinforces the importance of considering the historical ecology of an ecosystem and the utility of the fossil record in providing a historical perspective on long-term faunal changes.

We set out to describe the prevalence of Salmonella enterica in three large, adjacent cattle operations in the southern High Plains of the United States. Operations included two dairies (one of which routinely administers a commercially available Salmonella vaccine) and one feedlot. Samples were collected monthly for 12 months. At each sample collection, 25 freshly voided fecal pats and a sample from each of the water troughs were collected from each of five pens of cattle within an operation. Each monthly collection included a total of 375 fecal and ~32 water samples for a yearly total of 4,500 and 379 samples, respectively (note that the number of water troughs per pen varied within an operation). Salmonella was commonly recovered from fecal (71.3%) and water (28.5%) samples and tended to follow somewhat similar temporal patterns over time. However, its prevalence varied among operations despite being adjacent properties in that Salmonella was recovered from 61.3, 80.1, and 75% of fecal samples from dairy 1, dairy 2 and the feedlot, respectively. Salmonella prevalence in water samples across collection times averaged 36.1, 70.2, and 46.1% for dairy 1, dairy 2, and the feedlot, respectively. While it is uncertain why the Salmonella prevalence varied from operation to operation, the higher observed prevalence of Salmonella in water on dairy 2 and/or the use of a commercial Salmonella vaccine by dairy 1 may offer a partial explanation.

Growing empirical evidence indicates that financial anxiety causes reductions in short-term cognitive capacity. Results from urban communities in Delhi, India show sizable differences in the number of health events recalled between the poor and non-poor respondents over experimentally controlled recall periods. One explanation for this recall difference is 'poor memory'. Such results provide additional reasons for healthy skepticism of the accuracy of self-reported health survey data. The present research identifies which forms of cognitive capacity are related to health event recall and assesses the roles of poverty and illiteracy as mediating variables. Results indicate that underreporting of health events among the poor in rural Kenya is not solely due to 'poor memory'. Data used comes from a repeated cross-sectional study conducted in Samburu county, Kenya over 10-months between 2017-2018. This period coincided with the ending of a protracted and severe drought in East Africa. The results presented in the current study confirm the poor and non-poor distinction, but provide a more detailed cognitive explanation for such results. Reflective throught, as measured by fluid intelligence and heuristic use, is shown to be good predictors of fever recall among relatively poor rura communities in central Kenya.

Antimicrobial stewardship encourages appropriate antibiotic use, the specific activities of which will vary by institutional context. We investigated regional variation in antibiotic use by surveying three regional public hospitals in Kenya. Hospital-level data for antimicrobial stewardship activities, infection prevention and control, and laboratory diagnostic capacities were collected from hospital administrators, heads of infection prevention and control units, and laboratory directors, respectively. Patient-level antibiotic use data were abstracted from medical records using a modified World Health Organization point-prevalence survey form. Altogether, 1,071 consenting patients were surveyed at Kenyatta National Hospital (KNH, n = 579), Coast Provincial General Hospital (CPGH, n = 229) and Moi Teaching and Referral Hospital (MTRH, n = 263). The majority (67%, 722/1071) were ≥18 years and 53% (563/1071) were female. Forty-six percent (46%, 489/1071) were receiving at least one antibiotic. Antibiotic use was higher among children

Extended-spectrum-β-lactamase (ESBL) and AmpC-lactamase-producing Enterobacteriaceae are serious public health threats. Due to an increasing number of reports of ESBL and AmpC producing Escherichia coli in agricultural settings, it is critical to understand the relationship between the use of two of the highest priority critically important human antibiotics (e.g., third generation cephalosporins [3GC] and macrolides) in food animals and their potential contribution to the selection of ESBL/AmpC E. coli. The objective of our randomized controlled feedlot trial was to measure the effects of ceftiofur crystalline-free acid and tulathromycin on 3GC resistant fecal E. coli populations in cattle before and at various time points after treatment up to and including at slaughter. Multi-level mixed-effects linear regression showed no effect of ceftiofur and tulathromycin on 3GC E. coli CFU counts at slaughter (Day 99); however, a significant (p < 0.05) population shift was observed from susceptible to 3GC resistant E. coli immediately after ceftiofur administration (Day 7). Among 799 fecal samples screened using selective media, 17.7% were ESBL/AmpC E. coli positive, which were further tested for phenotypic antibiotic susceptibility. The majority of the isolates from these plates were multidrug-resistant (94.3%) and expressed either AmpC (78.1%) or ESBL (28.1%) phenotype. A subset of isolates was whole-genome sequenced (n = 20) and identified to harbor chromosomal and/or plasmidal bla genes such as CMY-2, CTX-M, and TEM. Our findings show a time-dependent selection of antibiotics on 3GC-resistant E. coli. High prevalence of multidrug-resistant ESBL/AmpC E. coli found in cattle feces highlights the importance of prudent use of antibiotics in livestock.

Abstract Background Vagus nerve activation impacts inflammation. Therefore, we hypothesized that vagal nerve stimulation (VNS) influenced arterial wall inflammation as measured by 18F-FDG uptake. Results Ten patients with left-sided VNS for refractory epilepsy were studied during stimulation (VNS-on) and in the hours after stimulation was switched off (VNS-off). In nine patients, 18F-FDG uptake was measured in the right carotid artery, aorta, bone marrow, spleen, and adipose tissue. Target-to-background ratios (TBRs) were calculated to normalize the respective standardized uptake values (SUVs) for venous blood pool activity. Median values are shown with interquartile range and compared using the Wilcoxon signed-rank test. Arterial SUVs tended to be higher during VNS-off than VNS-on [SUVmax all vessels 1.8 (1.5–2.2) vs. 1.7 (1.2–2.0), p = 0.051]. However, a larger difference was found for the venous blood pool at this time point, reaching statistical significance in the vena cava superior [meanSUVmean 1.3 (1.1–1.4) vs. 1.0 (0.8–1.1); p = 0.011], resulting in non-significant lower arterial TBRs during VNS-off than VNS-on. Differences in the remaining tissues were not significant. Insulin levels increased after VNS was switched off [55.0 pmol/L (45.9–96.8) vs. 48.1 pmol/L (36.9–61.8); p = 0.047]. The concurrent increase in glucose levels was not statistically significant [4.8 mmol/L (4.7–5.3) vs. 4.6 mmol/L (4.5–5.2); p = 0.075]. Conclusions Short-term discontinuation of VNS did not show a consistent change in arterial wall 18F-FDG-uptake. However, VNS did alter insulin and 18F-FDG blood levels, possibly as a result of sympathetic activation.

Abstract Background Achieving the Sustainable Development Goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires innovative control strategies. This proof-of-concept study examined the effectiveness of integrating control programs for two NTDs: mass drug administration (MDA) for soil-transmitted helminths in humans and mass dog rabies vaccination (MDRV). Methods The study was carried out in 24 Tanzanian villages. The primary goal was to demonstrate the feasibility of integrating community-wide MDA for STH and MDRV for rabies. The objectives were to investigate the popularity, participation and cost and time savings of integrated delivery, and to investigate the reach of the MDA with respect to primary school-aged children and other community members. To implement, we randomly allocated villages for delivery of MDA and MDRV (Arm A), MDA only (Arm B) or MDRV only (Arm C). Results Community support for the integrated delivery was strong (e.g. 85% of focus group discussions concluded that it would result in people getting “two for one” health treatments). A high proportion of households participated in the integrated Arm A events (81.7% MDA, 80.4% MDRV), and these proportions were similar to those in Arms B and C. These findings suggest that coverage might not be reduced when interventions are integrated. Moreover, in addition to time savings, integrated delivery resulted in a 33% lower cost per deworming dose and a 16% lower cost per rabies vaccination. The median percentage of enrolled primary school children treated by this study was 76%. However, because 37% of the primary school aged children that received deworming treatment were not enrolled in school, we hypothesize that the employed strategy could reach more school-aged children than would be reached through a solely school-based delivery strategy. Conclusions Integrated delivery platforms for health interventions can be feasible, popular, cost and time saving. The insights gained could be applicable in areas of sub-Saharan Africa that are remote or underserved by health services. These results indicate the utility of integrated One Health delivery platforms and suggest an important role in the global campaign to reduce the burden of NTDs, especially in hard-to-reach communities. Trial registration clinicaltrials.gov NCT03667079, retrospectively registered 11th September 2018.

Within the mouth bacteria are starved of saccharides as their main nutrient source between meals and it is unclear what drives their metabolism. Previously oral in vitro biofilms grown in saliva have shown proteolytic degradation of salivary proteins and increased extracellular proline. Although arginine and glucose have been shown before to have an effect on oral biofilm growth and activity, there is limited evidence for proline. Nuclear magnetic resonance (NMR) spectroscopy was used to identify extracellular metabolites produced by bacteria in oral biofilms grown on hydroxyapatite discs. Biofilms were inoculated with stimulated whole mouth saliva and then grown for 7 days using sterilized stimulated whole mouth saliva supplemented with proline, arginine or glucose as a growth-medium. Overall proline had a beneficial effect on biofilm growth—with significantly fewer dead bacteria present by biomass and surface area of the biofilms (p < 0.05). Where arginine and glucose significantly increased and decreased pH, respectively, the pH of proline supplemented biofilms remained neutral at pH 7.3–7.5. SDS-polyacrylamide gel electrophoresis of the spent saliva from proline and arginine supplemented biofilms showed inhibition of salivary protein degradation of immature biofilms. NMR analysis of the spent saliva revealed that proline supplemented biofilms were metabolically similar to unsupplemented biofilms, but these biofilms actively metabolized proline to 5-aminopentanoate, butyrate and propionate, and actively utilized glycine. This study shows that in a nutrient limited environment, proline has a beneficial effect on in vitro oral biofilms grown from a saliva inoculum.

In several developing countries, studies on antimicrobial resistance among bacteria from food animals are rare mostly because of under-resourced laboratories. The objective of this study was to develop and field-test a low cost protocol to estimate the isolate- and sample-level prevalence of resistance to critically important antibiotics among Escherichia coli and Salmonella isolated from dairy cattle feces. Using a predesigned protocol, fecal samples were collected to isolate non-type-specific E. coli and Salmonella using selective media without antibiotic supplements. Besides, samples were screened for E. coli and Salmonella isolates not susceptible to third-generation cephalosporins and quinolones using selective media supplemented with cefotaxime (1.0 μg/mL) and ciprofloxacine (0.5 μg/mL), respectively. All bacterial isolates were further tested for antibiotic susceptibility using disk diffusion. Bacterial isolates not susceptible to third-generation cephalosporins were tested for extended spectrum beta-lactamase (ESBL) phenotype using the combination disk test. Molecular methods were performed on selected bacterial isolates to identify and distinguish genetic determinants associated with the observed phenotypes. Among 85 non-type-specific E. coli isolated from MacConkey agar without antibiotics, the isolate-level prevalence of resistance to tetracycline was the highest (8.2%). Among 37 E. coli recovered from MacConkey agar with cefotaxime, 56.8% were resistant ceftriaxone. Among 22 E. coli isolates recovered from MacConkey agar with ciprofloxacin, 77.3% and 54.5% were resistant to nalidixic acid and ciprofloxacin, respectively. Sixteen Salmonella were isolated and only one demonstrated any resistance (i.e., single resistance to streptomycin). Among E. coli isolates not susceptible to ceftriaxone, an AmpC phenotype was more common than an ESBL phenotype (29 versus 10 isolates, respectively). Whole genome sequencing showed that phenotypic profiles of antibiotic resistance detected were generally substantiated by genotypic profiles. The tested protocol is suited to detecting and estimating prevalence of antimicrobial resistance in bacteria isolated from food animal feces in resource-limited laboratories in the developing world.

BackgroundPoultry represent a widely held economic, nutritional, and sociocultural asset in rural communities worldwide. In a recent longitudinal study in western Kenya, the reported mean number of chickens per household was 10, with increases in flock size constrained principally by mortality. Newcastle disease virus is a major cause of chicken mortality globally and hypothesized to be responsible for a large part of mortality in smallholder flocks. Our goal was to determine the impact of routine Newcastle disease virus (NDV) vaccination on flock size and use this data to guide programs to improve small flock productivity.MethodsWe conducted a factorial randomized controlled trial in 537 households: in 254 households all chickens were vaccinated every 3 months with I-2 NDV vaccine while chickens in 283 households served as unvaccinated controls. In both arms of the trial, all chickens were treated with endo- and ecto parasiticides every 3 months. Data on household chicken numbers and reported gains and losses were collected monthly for 18 months.ResultsConsistent with prior studies, the overall flock size was small but with increases in both arms of the study over time. The mean number of chickens owned at monthly census was 13.06±0.29 in the vaccinated households versus 12.06±0.20 in the control households (p = 0.0026) with significant gains in number of chicks (p = 0.06), growers (p = 0.09), and adults (p = 0.03) in the vaccinated flocks versus the controls. Household reported gains were 4.50±0.12 total chickens per month when vaccinated versus 4.15±0.11 in the non-vaccinated controls (p = 0.03). Gains were balanced by voluntary decreases, reflecting household decision-making for sales or household consumption, which were marginally higher, but not statistically significant, in vaccinated households and by involuntary losses, including mortality and loss due to predation, which were marginally higher in control households.ConclusionQuarterly NDV vaccination and parasiticidal treatment resulted in an increase in flock size by a mean of one bird per household as compared to households where the flock received only parasiticidal treatment. While results suggest that the preventable fraction of mortality attributable to Newcastle disease is comparatively small relatively to all-cause mortality in smallholder households, there was a significant benefit to vaccination in terms of flock size. Comparison with previous flock sizes in the study households indicate a more significant benefit from the combined vaccination and parasiticidal treatment, supporting a comprehensive approach to improving flock health and improving household benefits of production in the smallholder setting.