Tick exposure biomarkers: A One Health approach to new tick surveillance tools.

The spread of tick-borne disease (TBD) is escalating globally, driven by climate change and socio-economic shifts, underlining the urgency to improve surveillance, diagnostics, and control strategies. Ticks can transmit a range of pathogens increasing the risk of transmission of human and veterinary diseases such as Lyme disease, tick-borne encephalitis, theileriosis, anaplasmosis, or Crimean-Congo hemorrhagic fever. Surveillance methods play a crucial role in monitoring the spread of tick-borne pathogens (TBP). However, there are shortcomings in the current surveillance methods regarding risks related to ticks. Human-tick encounters offer a novel metric for disease risk assessment, integrating human behavior into traditional surveillance models. However, to more reliably measure tick exposure, a molecular marker is needed. The identification of antibodies against arthropod salivary proteins as biomarkers for vector exposure represents a promising avenue for enhancing existing diagnostic and surveillance metrics. Here we explore how the use of tick saliva biomarkers targeting recombinant proteins and synthetic peptides could significantly improve the assessment of TBD transmission risk and the effectiveness of vector control measures. With focused efforts on creating a biomarker against tick exposure suitable for humans and domestic animals alike, tick surveillance, diagnosis and control would be more achievable and aid in reducing the mounting threat of TBP through a One Health lens.

Analysis of crude wastewater from two treatment plants in South Wales for 35 new psychoactive substances and cocaine, and cannabis.

This study investigates the presence of new psychoactive substances (NPS) and their metabolites in two wastewater treatment plants (WWTPs) situated in South Wales, UK (WWTP-1 and WWTP-2). Analysis was conducted for 35 NPS and metabolites, along with the inclusion of benzoylecgonine (main cocaine metabolite) and cannabis, the most detected illicit substances. Benzoylecgonine was identified as the predominant substance in both WWTPs. Epidemiological calculations revealed the average population consumption of cocaine to be 3.88 mg/d/1000 inhabitants around WWTP-1 and 1.97 mg/d/1000 inhabitants for WWTP-2. The removal efficiency of benzoylecgonine across both WWTPs was observed at an average of 73%. Subsequent qualitative analyses on randomly selected wastewater samples detected medicinal compounds including buprenorphine, methadone, and codeine in both WWTPs. An additional experiment employing enzymatic hydrolysis revealed the presence of morphine, an increased presence of codeine, and 11-Nor-9-Carboxy-THC (THC-COOH) post-hydrolysis. These findings underscore the significant presence of illicit substances and medicinal compounds in wastewater systems with the absence of NPS within the South Wales area, highlighting the necessity for enhanced monitoring and treatment strategies to address public health and environmental concerns.

Current and lagged associations of meteorological variables and Aedes mosquito indices with dengue incidence in the Philippines.

BACKGROUND: Dengue is an increasing health burden that has spread throughout the tropics and sub-tropics. There is currently no effective vaccine and control is only possible through integrated vector management. Early warning systems (EWS) to alert potential dengue outbreaks are currently being explored but despite showing promise are yet to come to fruition. This study addresses the association of meteorological variables with both mosquito indices and dengue incidences and assesses the added value of additionally using mosquito indices for predicting dengue incidences. METHODOLOGY/PRINCIPAL FINDINGS: Entomological surveys were carried out monthly for 14 months in six sites spread across three environmentally different cities of the Philippines. Meteorological and dengue data were acquired. Non-linear generalized additive models were fitted to test associations of the meteorological variables with both mosquito indices and dengue cases. Rain and the diurnal temperature range (DTR) contributed most to explaining the variation in both mosquito indices and number of dengue cases. DTR and minimum temperature also explained variation in dengue cases occurring one and two months later and may offer potentially useful variables for an EWS. The number of adult mosquitoes did associate with the number of dengue cases, but contributed no additional value to meteorological variables for explaining variation in dengue cases. CONCLUSIONS/SIGNIFICANCE: The use of meteorological variables to predict future risk of dengue holds promise. The lack of added value of using mosquito indices confirms several previous studies and given the onerous nature of obtaining such information, more effort should be placed on improving meteorological information at a finer scale to evaluate efficacy in early warning of dengue outbreaks.

Stability of new psychoactive substances in crude wastewater.

Those involved in drug testing continue to grapple with the dynamic nature of emerging psychoactive substances (NPS) and their rapid infiltration into society. The challenge extends beyond merely detecting and measuring NPS using analytical tools; it also encompasses the complexities arising from the formation and presence of metabolites and degradation products. This study utilises liquid chromatography time-of-flight mass spectrometry to investigate the stability of new psychoactive substances in wastewater. Seven NPS compounds including 25C-NBOMe, 5F-APINACA 4-hydroxyphenyl, AB-PINACA, APINACA 4-hydroxyphenyl, fentanyl, norfentanyl and MDPV, along with their corresponding internal standard, were examined. Reference material for each NPS compound was introduced into a wastewater sample from a Wessex water treatment plant. The sample was then exposed to four different environments: room temperature, refrigerator temperature, acidification to pH 2, and the introduction of sodium metabisulfite. The findings highlight the critical dependence of storage conditions on target analytes, emphasizing the paramount importance of the time elapsed between collection and analysis for NPS wastewater analysis. Notably, synthetic cannabinoids exhibit limited stability in wastewater whereas cathinone-like substances demonstrate greater stability. Furthermore, metabolites prove to be more stable in wastewater than the parent drug, suggesting that focusing on metabolite detection may be more favourable for future analysis.

Update on tick-borne pathogens detection methods within ticks.

Ticks are known vectors of various pathogens, including bacteria, parasites and viruses, that impact both animal and human health. Improving knowledge of the distribution of tick-borne pathogens, combined with their early detection in ticks, are essential steps to fight against tick-borne diseases and mitigate their impacts. Here we give an overview of what are the common methods of pathogen detection in tick samples, including recent developments concerning how to handle tick samples, get access to tick-borne pathogens by chemical or physical disruption of the ticks, and methods used for the RNA/DNA extraction steps. Furthermore, we discuss promising tools that are developed for other sample types such as serum or blood to detect tick-borne pathogens, and those that could be used in the future for tick samples.

hopsy - a methods marketplace for convex polytope sampling in Python.

SUMMARY: Effective collaboration between developers of Bayesian inference methods and users is key to advance our quantitative understanding of biosystems. We here present hopsy, a versatile open-source platform designed to provide convenient access to powerful Markov chain Monte Carlo sampling algorithms tailored to models defined on convex polytopes (CP). Based on the high-performance C++ sampling library HOPS, hopsy inherits its strengths and extends its functionalities with the accessibility of the Python programming language. A versatile plugin-mechanism enables seamless integration with domain-specific models, providing method developers with a framework for testing, benchmarking, and distributing CP samplers to approach real-world inference tasks. We showcase hopsy by solving common and newly composed domain-specific sampling problems, highlighting important design choices. By likening hopsy to a marketplace, we emphasize its role in bringing together users and developers, where users get access to state-of-the-art methods, and developers contribute their own innovative solutions for challenging domain-specific inference problems. AVAILABILITY AND IMPLEMENTATION: Sources, documentation and a continuously updated list of sampling algorithms are available at https://jugit.fz-juelich.de/IBG-1/ModSim/hopsy, with Linux, Windows and MacOS binaries at https://pypi.org/project/hopsy/.

A review on nanomaterial-based SERS substrates for sustainable agriculture.

The agricultural sector plays a pivotal role in driving the economy of many developing countries. Any dent in this economical structure may have a severe impact on a country's population. With rising climate change and increasing pollution, the agricultural sector is experiencing significant damage. Over time this cumulative damage will affect the integrity of food crops and create food security issues around the world. Therefore, an early warning system is needed to detect possible stress on food crops. Here we present a review of the recent developments in nanomaterial-based Surface Enhanced Raman Spectroscopy (SERS) substrates which could be utilized to monitor agricultural crop responses to natural and anthropogenic stress. Initially, our review delves into diverse and cost-effective strategies for fabricating SERS substrates, emphasizing their intelligent utilization across various agricultural scenarios. In the second phase of our review, we spotlight the specific application of SERS in addressing critical food security issues. By detecting nutrients, hormones, and effector molecules in plants, SERS provides valuable insights into plant health. Furthermore, our exploration extends to the detection of contaminants, chemicals, and foodborne pathogens within plants, showcasing the versatility of SERS in ensuring food safety. The cumulative knowledge derived from these discussions illustrates the transformative potential of SERS in bolstering the agricultural economy. By enhancing precision in nutrient management, monitoring plant health, and enabling rapid detection of harmful substances, SERS emerges as a pivotal tool in promoting sustainable and secure agricultural practices. Its integration into agricultural processes not only augments productivity but also establishes a robust defence against potential threats to crop yield and food quality. As SERS continues to evolve, its role in shaping the future of agriculture becomes increasingly pronounced, promising a paradigm shift in how we approach and address challenges in food production and safety.

Potential of Synbiotics and Probiotics as Chemopreventive Agent.

Cancer remains a global problem, with millions of new cases diagnosed yearly and countless lives lost. The financial burden of cancer therapy, along with worries about the long-term safety of existing medicines, necessitates the investigation of alternative approaches to cancer prevention. Probiotics generate chemopreventive compounds such as bacteriocins, short-chain fatty acids (SCFA), and extracellular polymeric substances (EPS), which have demonstrated the ability to impede cancer cell proliferation, induce apoptosis, and bolster the expression of pro-apoptotic genes. On the other hand, prebiotics, classified as non-digestible food ingredients, promote the proliferation of probiotics within the colon, thereby ensuring sustained functionality of the gut microbiota. Consequently, the synergistic effect of combining prebiotics with probiotics, known as the synbiotic effect, in dietary interventions holds promise for potentially mitigating cancer risk and augmenting preventive measures. The utilization of gut microbiota in cancer treatment has shown promise in alleviating adverse health effects. This review explored the potential and the role of probiotics and synbiotics in enhancing health and contributing to cancer prevention efforts. In this review, the applications of functional probiotics and synbiotics, the mechanisms of action of probiotics in cancer, and the relationship of probiotics with various drugs were discussed, shedding light on the potential of probiotics and synbiotics to alleviate the burdens of cancer treatment.

Increased ß2-adrenergic signaling promotes fracture healing through callus neovascularization in mice.

Traumatic brain injury (TBI) leads to skeletal changes, including bone loss in the unfractured skeleton, and paradoxically accelerates healing of bone fractures; however, the mechanisms remain unclear. TBI is associated with a hyperadrenergic state characterized by increased norepinephrine release. Here, we identified the ß2-adrenergic receptor (ADRB2) as a mediator of skeletal changes in response to increased norepinephrine. In a murine model of femoral osteotomy combined with cortical impact brain injury, TBI was associated with ADRB2-dependent enhanced fracture healing compared with osteotomy alone. In the unfractured 12-week-old mouse skeleton, ADRB2 was required for TBI-induced decrease in bone formation and increased bone resorption. Adult 30-week-old mice had higher bone concentrations of norepinephrine, and ADRB2 expression was associated with decreased bone volume in the unfractured skeleton and better fracture healing in the injured skeleton. Norepinephrine stimulated expression of vascular endothelial growth factor A and calcitonin gene-related peptide-α (αCGRP) in periosteal cells through ADRB2, promoting formation of osteogenic type-H vessels in the fracture callus. Both ADRB2 and αCGRP were required for the beneficial effect of TBI on bone repair. Adult mice deficient in ADRB2 without TBI developed fracture nonunion despite high bone formation in uninjured bone. Blocking ADRB2 with propranolol impaired fracture healing in mice, whereas the ADRB2 agonist formoterol promoted fracture healing by regulating callus neovascularization. A retrospective cohort analysis of 72 patients with long bone fractures indicated improved callus formation in 36 patients treated with intravenous norepinephrine. These findings suggest that ADRB2 is a potential therapeutic target for promoting bone healing.

Unveiling Morphine: A Rapid and Selective Fluorescence Sensor for Forensic and Medical Analysis.

Opioid use, particularly morphine, is linked to CNS-related disorders, comorbidities, and premature death. Morphine, a widely abused opioid, poses a significant global health threat and serves as a key metabolite in various opioids. Here, we present a turn-off fluorescent sensor capable of detecting morphine with exceptional sensitivity and speed in various samples. The fluorescent sensor was developed through the dimerization process of 7-methoxy-1-tetralone and subsequent demethylation to produce the final product. Despite morphine possessing inherent fluorophoric properties and emitting light in an approximately similar wavelength as the sensor's fluorescent blue light, the introduction of the target molecule (morphine) in the presence of the sensor caused a reduction in the sensor's fluorescence intensity, which is attributable to the formation of the sensor-morphine complex. By utilizing this fluorescence quenching sensor, the chemo-selective detection of morphine becomes highly feasible, encompassing a linear range from 0.008 to 40 ppm with an impressive limit of detection of 8 ppb. Consequently, this molecular probe demonstrates a successful application in determining trace amounts of morphine within urine, yielding satisfactory analytical results. The study also explores the effect of several variables on the sensor's response and optimizes the detection of morphine in urine using a response surface methodology with a central composite design.

Transcript-dependent effects of the CALCA gene on the progression of post-traumatic osteoarthritis in mice.

Osteoarthritis represents a chronic degenerative joint disease with exceptional clinical relevance. Polymorphisms of the CALCA gene, giving rise to either a procalcitonin/calcitonin (PCT/CT) or a calcitonin gene-related peptide alpha (αCGRP) transcript by alternative splicing, were reported to be associated with the development of osteoarthritis. The objective of this study was to investigate the role of both PCT/CT and αCGRP transcripts in a mouse model of post-traumatic osteoarthritis (ptOA). WT, αCGRP-/- and CALCA-/- mice were subjected to anterior cruciate ligament transection (ACLT) to induce ptOA of the knee. Mice were sacrificed 4 and 8 weeks post-surgery, followed by micro-CT and histological evaluation. Here we show that the expression of both PCT/CT and αCGRP transcripts is induced in ptOA knees. CALCA-/- mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers compared to αCGRP-/- and WT mice. Osteophyte formation is reduced to the same extent in CALCA-/- and αCGRP-/- mice compared to WT controls, while a reduced synovitis score is noticed exclusively in mice lacking CALCA. Our data show that expression of the PCT/CT transcript protects from the progression of ptOA, while αCGRP promotes osteophyte formation, suggesting that CALCA-encoded peptides may represent novel targets for the treatment of ptOA.

Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis.

BACKGROUND AND AIMS: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. METHODS: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. RESULTS: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. CONCLUSIONS: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

Absence of new psychoactive substances in wastewater from South Wales, UK, revealed by optimised liquid chromatography-time-of-flight analysis.

New psychoactive substances are produced and marketed to mimic the effects of their illicit counterparts and to attempt to evade drug tests and prosecution. Here, we present the optimisation, validation and application of an analytical method using liquid chromatography-time-of-flight mass spectrometry to detect and quantify 37 new psychoactive substances and illicit substances in wastewater from South Wales, UK, using a targeted analysis method. Sample preparation was performed using solid-phase extraction with Oasis HLB cartridges. The LC separation was performed using a YMC-Triart Phenyl 450 bar column (12 nm, 5 µm, 100 × 3 mm) which provided good separation and resolution for all targeted analytes with a run time of 9 min. The method was validated using the following parameters: sensitivity, selectivity, linearity, accuracy, precision, recovery and matrix effects. The method was then applied to influent wastewater samples collected from two wastewater treatment plants in Wales, UK.

Slaughterhouse by-products composting: can microorganisms inoculum addition mitigate final compost odor emission?

Small slaughterhouses generate biowaste, which for economic reasons, is generally destined for composting. Inoculating appropriate microorganisms can improve biodegradation efficiency and mitigate odor generation during the composting process and can give rise to composts with neutral or pleasant odors. Therefore, the aim of this study was to compare the odor intensity reduction of compost generated with and without a formulated inoculum (Saccharomyces cerevisiae, Bacillus subtilis, and Rhodopseudomonas palustris). A set of experimental data was collected and analyzed according to the German "Verein Deutscher Ingenieure" odor protocol. The results showed that adding microorganisms was effective in reducing unpleasant odors in all three composts generated from swine, cattle, and poultry slaughterhouse by-products during both summer and winter seasons. Additionally, soil odor was predominant in composts that were inoculated in the two tested seasons (i.e., summer and winter). On the other hand, composts without inoculation had odors similar to peat for swine compost, ammonia for cattle compost, and manure for poultry compost, regardless of the season tested. Overall, composting process with appropriate inoculum can help in the correct disposal of slaughterhouse wastes by transforming organic matter into composts, which can have economic and environmental value as a soil conditioner and/or fertilizer.

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice.

BACKGROUND: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression. PURPOSE: To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice. STUDY DESIGN: Controlled laboratory study. METHODS: OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro-computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically. RESULTS: Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed. CONCLUSION: Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery. CLINICAL RELEVANCE: TXA might be beneficial in patients with posttraumatic OA of the knee.

Routine Metagenomics Service for ICU Patients with Respiratory Infection.

Rationale: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Objectives: Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. Methods: RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London. Measurements and Main Results: During the first 15 weeks, RMg provided same-day results for 110 samples (86%), with a median turnaround time of 6.7 hours (interquartile range = 6.1-7.5 h). RMg was 93% sensitive and 81% specific for clinically relevant pathogens compared with routine testing. Forty-eight percent of RMg results informed antimicrobial prescribing changes (22% escalation; 26% deescalation) with escalation based on speciation in 20 out of 24 cases and detection of acquired-resistance genes in 4 out of 24 cases. Fastidious or unexpected organisms were reported in 21 samples, including anaerobes (n = 12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus, and Legionella pneumophila ST1326, which was subsequently isolated from the bedside water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A), and Aspergillus fumigatus with multiple treatments and public health impacts. Conclusions: This pilot study illustrates the potential of RMg testing to provide benefits for antimicrobial treatment, infection control, and public health when provided in a real-world critical care setting. Multicenter studies are now required to inform future translation into routine service.

Identification of novel small RNAs in extracellular vesicles produced by Actinobacillus pleuropneumoniae.

Extracellular vesicle (EV) production by bacteria is an important mechanism for microbial communication and host-pathogen interaction. EVs of some bacterial species have been reported to contain nucleic acids. However, the role of small RNAs (sRNAs) packaged in EVs is poorly understood. Here, we report on the RNA cargo of EVs produced by the pig pathogen Actinobacillus pleuropneumoniae, the causal agent of porcine pleuropneumonia, a disease which causes substantial economic losses to the swine industry worldwide. The EVs produced by aerobically and anaerobically grown bacteria were only slightly different in size and distribution. Total cell and outer membrane protein profiles and lipid composition of A. pleuropneumoniae whole cell extracts and EVs were similar, although EVs contained rough lipopolysaccharide compared to the smooth form in whole cells. Approximately 50% of Galleria mellonella larvae died after the injection of EVs. RNAseq, RT-PCR, protection from nuclease degradation, and database searching identified previously described and 13 novel A. pleuropneumoniae sRNAs in EVs, some of which were enriched compared to whole cell content. We conclude that A. pleuropneumoniae EVs contain sRNAs, including those known to be involved in virulence, and some with homologs in other Pasteurellaceae and/or non-Pasteurellaceae. Further work will establish whether the novel sRNAs in A. pleuropneumoniae EVs play any role in pathogenesis.

Wastewater analysis for new psychoactive substances and cocaine and cannabis in a Northern Ireland Prison.

The global drug market has been significantly impacted by the emergence of new psychoactive substances, leading to challenges in creating effective legislative controls and their use within recreational drug consumption. This research explores the prevalence of new psychoactive substances and non-medicinal and medicinal compounds within a prison facility in Northern Ireland. Wastewater samples collected from seven different manholes within the prison were analysed for 37 target compounds including the two most found illicit substances: benzoylecgonine (primary metabolite of cocaine) and cannabis. Using solid phase extraction with Oasis HLB and liquid-chromatography-time-of-flight-mass spectrometry across a gradient of 9 min, our analysis revealed that benzoylecgonine was the sole compound consistently present in all collected samples. Following this finding, our target compound selection was broadened to encompass medicinal compounds and employing qualitative analysis we re-evaluated the samples and discovered the presence of buprenorphine, benzodiazepines, methadone, morphine, and codeine. Finally, the study explored the application of enzymatic beta-glucuronidase hydrolysis to the samples. This final phase yielded significant findings, indicating the presence of codeine and nordiazepam at higher peak intensities, thereby shedding light on the potential implications of this enzymatic process.

The selective norepinephrine reuptake inhibitor reboxetine promotes late-stage fracture healing in mice.

Impaired fracture healing is of high clinical relevance, as up to 15% of patients with long-bone fractures display non-unions. Fracture patients also include individuals treated with selective norepinephrine reuptake inhibitors (SNRI). As SNRI were previously shown to negatively affect bone homeostasis, it remained unclear whether patients with SNRI are at risk of impaired bone healing. Here, we show that daily treatment with the SNRI reboxetine reduces trabecular bone mass in the spine but increases cortical thickness and osteoblast numbers in the femoral midshaft. Most importantly, reboxetine does not impair bone regeneration in a standardized murine fracture model, and even improves callus bridging and biomechanical stability at late healing stages. In sum, reboxetine affects bone remodeling in a site-specific manner. Treatment does not interfere with the early and intermediate stages of bone regeneration and improves healing outcomes of the late-stage fracture callus in mice.

The 2013 Chikungunya outbreak in the Caribbean was structured by the network of cultural relationships among islands.

In 2013, the Caribbean underwent an unprecedented epidemic of Chikungunya that affected 29 islands and mainland territories throughout the Caribbean in the first six months. Analysing the spread of the epidemic among the Caribbean islands, we show that the initial patterns of the epidemic can be explained by a network model based on the flight connections among islands. The network does not follow a random graph model and its topology is likely the product of geo-political relationships that generate increased connectedness among locations sharing the same language. Therefore, the infection propagated preferentially among islands that belong to the same cultural domain, irrespective of their human and vector population densities. Importantly, the flight network topology was also a more important determinant of the disease dynamics than the actual volume of traffic. Finally, the severity of the epidemic was found to depend, in the first instance, on which island was initially infected. This investigation shows how a simple epidemic model coupled with an appropriate human mobility model can reproduce the observed epidemiological dynamics. Also, it sheds light on the design of interventions in the face of the emergence of infections in similar settings of naive subpopulations loosely interconnected by host movement. This study delves into the feasibility of developing models to anticipate the emergence of vector-borne infections, showing the importance of network topology, bringing valuable methods for public health officials when planning control policies. Significance statement: The study shows how a simple epidemic model associated with an appropriate human mobility model can reproduce the observed epidemiological dynamics of the 2014 Chikungunya epidemic in the Caribbean region. This model sheds light on the design of interventions in the face of the emergence of infections in similar settings of naive subpopulations loosely interconnected by the host.