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Abstract Background Antibiotic resistance (ABR) has emerged as a major threat to health. Properly informed decisions to mitigate this threat require surveillance systems that integrate information on resistant bacteria and antibiotic use in humans, animals, and the environment, in line with the One Health concept. Despite a strong call for the implementation of such integrated surveillance systems, we still lack a comprehensive overview of existing organizational models for integrated surveillance of ABR. To address this gap, we conducted a scoping review to characterize existing integrated surveillance systems for ABR. Methods The literature review was conducted using the PRISMA guidelines. The selected integrated surveillance systems were assessed according to 39 variables related to their organization and functioning, the socio-economic and political characteristics of their implementation context, and the levels of integration reached, together with their related outcomes. We conducted two distinct, complementary analyses on the data extracted: a descriptive analysis to summarize the characteristics of the integrated surveillance systems, and a multiple-correspondence analysis (MCA) followed by a hierarchical cluster analysis (HCA) to identify potential typology for surveillance systems. Results The literature search identified a total of 1330 records. After the screening phase, 59 references were kept from which 14 integrated surveillance systems were identified. They all operate in high-income countries and vary in terms of integration, both at informational and structural levels. The different systems combine information from a wide range of populations and commodities -in the human, animal and environmental domains, collection points, drug-bacterium pairs, and rely on various diagnostic and surveillance strategies. A variable level of collaboration was found for the governance and/or operation of the surveillance activities. The outcomes of integration are poorly described and evidenced. The 14 surveillance systems can be grouped into four distinct clusters, characterized by integration level in the two dimensions. The level of resources and regulatory framework in place appeared to play a major role in the establishment and organization of integrated surveillance. Conclusions This study suggests that operationalization of integrated surveillance for ABR is still not well established at a global scale, especially in low and middle-income countries and that the surveillance scope is not broad enough to obtain a comprehensive understanding of the complex dynamics of ABR to appropriately inform mitigation measures. Further studies are needed to better characterize the various integration models for surveillance with regard to their implementation context and evaluate the outcome of these models.

The southern region of Madagascar experiences a series of crises related to agro-climatic, nutritional, security, institutional, and political conditions despite the presence of numerous development aid projects over several decades. To understand this apparent paradox, this scoping review examines 63 peer-reviewed and grey literature studies in both French and English from 1990 to 2023, focusing on project failures in the southern region of Madagascar. The article makes two main contributions. Firstly, in terms of methodology, it presents an original approach to conduct a scoping review in a geographical area characterized by the presence of numerous development players and a low number of scientific articles. Secondly, it represents the very first article to offer a synthesis of the literature analyzing development failures in southern Madagascar. It thus appears that the equilibrium of maldevelopment in southern Madagascar is rooted in the systemic interaction between agri-environmental tensions, the failures of the state and aid, and the inadequate consideration of socio-anthropological dimensions and gender relations.

Studies on the environmental impact of nanoplastics face challenges in plastic analysis and a scarcity of nanoplastic materials necessary for the development of analytical techniques and experiments on biota impact. Here we provide detailed procedures for obtaining nanoparticles suspended in water for the most commonly used polymers: Polypropylene (PP), Polyvinylchloride (PVC), Low- and High-Density Polyethylene (PE-LD, PE-HD), and Polystyrene (PS). We dissolved larger size material to reprecipitate nanoparticles. For all plastic types, we obtained nanoparticles with a size between 50 and 300 nm, and a mainly spherical morphology. We verified that no irreversible agglomeration or coalescence of the particles occurred after 5 days of storage. The concentrations obtained in the final carrier solution were of the order of 109 particles mL−1. To prevent the persistence of reagents in the final carrier solution, a filtration step was implemented at the end of the process. The method proved unsuitable for Polyethylene Terephthalate (PET).

Abstract Currently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin. The aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4). Transcutaneous penetration was evaluated by ex vivo studies on tape-stripped pig ear skin. ScFv and Ab visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied in vitro using HEK-Blue™ IL-4/IL-13 cells and normal human keratinocytes (NHKs). After 24 h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on the stratum corneum. In addition, the anti-hIL4 scFv showed very efficient and dose-dependent hIL-4 neutralization. Thus, scFv penetrates through to the upper papillary dermis while Ab mostly remains on the surface, the anti-hIL4 scFv also neutralizes its target effectively suggesting its potential use as topical therapy for AD.

Glyphosate is a broad-spectrum herbicide whose use is now restricted because of its potential toxicity to human and environmental health. Its presence is observed even in aquatic ecosystems where this emerging contaminant affects primary producers such as phytoplankton. This study focuses on the cosmopolitan green microalga, Chlorella vulgaris Beijerinck, 1890. The ecotoxicological effects of the commercial herbicide, Roundup®, were evaluated in freshwater (FW) and seawater (SW) using ultraviolet/visible spectroscopy over a five-day experiment. A dose-response relationship was investigated on a wide range of concentrations (0.1 to 25,000 µg L−1). The population of FW-Chlorella was stimulated when exposed to concentrations from 10 to 5,000 µg L−1 and inhibited otherwise. Chlorophylls and carotenoids exhibited their highest peak area values after four days, before their signal was depleted by day 5, regardless of Roundup® concentration. Conversely, cells of SW-Chlorella were stimulated at the highest concentrations (> 1 mg L−1), as if glyphosate was acting as a source of phosphorous nutrient. The peak areas of chlorophylls and carotenoids increased in the presence of the contaminant, especially on day 3. The defense mechanisms activated during its adaptation to marine salinity (e.g., decrease in the chlorophyll/carotenoid peak area ratio) could have favored its resilience. Exposure to Roundup® caused a shift in the wavelength at maximum absorbance, which could introduce a bias when measuring peak heights at a single wavelength. The analysis of absorption spectra and the use of peak areas appear to be a promising approach for monitoring changes in photosynthetic pigments.

We theoretically and numerically investigate the spin fluctuations induced in a thermal atomic ensemble by an external fluctuating uniaxial magnetic field, in the context of a standard spin noise spectroscopy (SNS) experiment. We show that additional spin noise is excited, which dramatically depends on the magnetic noise variance and bandwidth, as well as on the power of the probe light and its polarization direction. We develop an analytical perturbative model proving that this spin noise first emerges from the residual optical pumping in the medium, which is then converted into spin fluctuations by the magnetic noise and eventually detected using SNS. The system studied is a spin-1 system, which thus shows both Faraday rotation and ellipticity noises induced by the random magnetic fluctuations. The analytical model gives results in perfect agreement with the numerical simulations, with potential applications in future experimental characterization of stray field properties and their influence on spin dynamics.

Background & Aims: Hypothermic oxygenated machine perfusion (HOPE) is a promising technique for providing oxygen to the liver during graft preservation; however, because of associated logistical constraints, addition of an oxygen transporter to static cold-storage solutions (SCS) might be easier. M101 is marine worm haemoglobin that has been shown to improve kidney preservation in the clinic when added to SCS. This study evaluated the effects of the addition of M101 to SCS on the quality of pig liver graft preservation. Methods: Pig liver grafts were preserved using SCS, HOPE, or SCS+M101, and the liver functions were compared during cold preservation and after orthotopic allotransplantation (OLT) in pigs. Results: During preservation of the liver grafts, mitochondrial function, ATP synthesis, antioxidant capacities, and hepatocyte architecture were better preserved, and free radical production, antioxidant activities, and inflammatory mediators were lower, with HOPE or SCS+M101 than with SCS alone. However, after 1 h of preservation, liver functions with HOPE were superior to those with SCS+M101. After 6 h of preservation and OLT, blood levels of aspartate and alanine aminotransferases and lactate dehydrogenase increased with a peak effect at Day 1 post-transplant; values were similar with HOPE and SCS+M101, and were significantly lower than those in the SCS group. At Days 1 and 3, tumor necrosis factor α levels remained lower with HOPE and SCS+M101 vs. SCS. At Day 7, liver cell necrosis and inflammation were less marked in both oxygenated groups. Conclusions: When added to SCS, M101 effectively oxygenates liver grafts during preservation, preventing post-transplant injury; although graft performances are below those achieved with HOPE. Lay summary: When transported between donors and recipients, even cold-stored liver grafts need oxygen to maintain their viability. To provide them with oxygen, we added a marine worm super haemoglobin (M101) to the cold-storage solution UWCS. Using a pig liver transplant model, we revealed that livers cold stored with UWCS+M101 showed improved oxygenation compared with simple cold-storage solutions, but did not reach the oxygenation level achieved with machine perfusion.

Class switch recombination (CSR) changes antibody isotype by replacing Cμ constant exons with different constant exons located downstream on the immunoglobulin heavy (IgH) locus. During CSR, transcription through specific switch (S) regions and processing of non-coding germline transcripts (GLTs) are essential for the targeting of activation-induced cytidine deaminase (AID). While CSR to IgG1 is abolished in mice lacking an Iγ1 exon donor splice site (dss), many questions remain regarding the importance of I exon dss recognition in CSR. To further clarify the role of I exon dss in CSR, we first evaluated RNA polymerase II (RNA pol II) loading and chromatin accessibility in S regions after activation of mouse B cells lacking Iγ1 dss. We found that deletion of Iγ1 dss markedly reduced RNA pol II pausing and active chromatin marks in the Sγ1 region. We then challenged the post-transcriptional function of I exon dss in CSR by using antisense oligonucleotides (ASOs) masking I exon dss on GLTs. Treatment of stimulated B cells with an ASO targeting Iγ1 dss, in the acceptor Sγ1 region, or Iμ dss, in the donor Sμ region, did not decrease germline transcription but strongly inhibited constitutive splicing and CSR to IgG1. Supporting a global effect on CSR, we also observed that the targeting of Iμ dss reduced CSR to IgG3 and, to a lesser extent, IgG2b isotypes. Altogether, this study reveals that the recognition of I exon dss first supports RNA pol II pausing and the opening of chromatin in targeted S regions and that GLT splicing events using constitutive I exon dss appear mandatory for the later steps of CSR, most likely by guiding AID to S regions.

We perform spin noise spectroscopy experiments in metastable helium atoms at room temperature, with a probe light whose frequency is blue detuned from the D _0 line. Both circular birefringence fluctuations (Faraday noise) and linear birefringence fluctuations (ellipticity noise) are explored theoretically and experimentally. In particular, it is shown that in both cases but for different optical detunings, two noise resonances are isolated at the Larmor frequency and at twice the Larmor frequency with a behavior, which strongly depends on the orientation of the probe field polarization. The simple structure of metastable helium allows us to probe, model and explain the changes in the behavior of these peaks in terms of circular and linear dichroisms and birefringences as well as in terms of spin oscillation modes.

Oxygen (O2) is indispensable for aerobic respiration and cellular metabolism. In case of injury, reactive oxygen species are produced, causing oxidative stress, which triggers cell damaging chemical mediators leading to ischemic reperfusion injuries (IRI). Sufficient tissue oxygenation is necessary for optimal wound healing. In this context, several hemoglobin-based oxygen carriers have been developed and tested, especially as graft preservatives for transplant procedures. However, most of the commercially available O2 carriers increase oxidative stress and show some adverse effects. Interestingly, the hemoglobin derived from the marine lugworm Arenicola marina (M101) has been presented as an efficient therapeutic O2 carrier with potential anti-inflammatory, anti-bacterial, and antioxidant properties. Furthermore, it has demonstrated promise as a supplement to conventional organ preservatives by reducing IRI. This review summarizes the properties and various applications of M101. M101 is an innovative oxygen carrier with several beneficial therapeutic properties, and further research must be carried out to determine its efficacy in the management of different pathologies.

No posee resumen.

Objective: Physical therapy following traumatic brain injury (TBI) can be negatively impacted by psychological symptoms, atypical symptom reporting, and response bias. We examined rates of Symptom Validity Test (SVT) failure in active duty military service members with a history of mild-moderate TBI and its impact on gait speed. Setting: Intensive Outpatient Program at the National Intrepid Center of Excellence at Walter Reed National Military Medical Center. Participants: Participants were 84 active duty service members with a history of mild-moderate TBI classified as SVT pass (n = 49) or SVT fail (n = 35). Design: Retrospective study. Main Measures: Overground preferred and fast walking speed as well as Computer Assisted Rehabilitation Environment (CAREN) gait speed were recorded. Participants completed the Neurobehavioral Symptom Inventory and the Validity-10 was used to assign patients into the SVT pass and SVT fail groups. Gait speed metrics were compared across these groups and test operating characteristics were calculated. Results: Approximately 42% of the sample was classified into the SVT fail group. All 3 gait speed measures were significantly slower in the SVT fail group than in the SVT pass group (P s <.001, d s = 0.60-0.80). Gait speed cutoffs for screeners or indicators of atypical reporting were identified. Conclusions: The potential for response bias is a critical area for the clinician to consider when conducting physical therapy evaluations. Participants in the SVT fail group had slower walking speed on all 3 measures assessed. Several useful cutoffs were identified to serve as screeners or indicators of SVT failure, though these preliminary findings have limitations and need to be replicated. [ABSTRACT FROM AUTHOR]

Background: Porphyromonas gingivalis exacerbates tissue hypoxia and worsens periodontal inflammation. This study investigated the effect of a therapeutic oxygen carrier (M101), derived from Arenicola marina, on hypoxia and associated inflammation in the context of periodontitis.Methods: The effect of M101 on GLUT-1, GLUT-3, HIF-1α, and MMP-9 expression, hypoxia, and antioxidant status in oral epithelial cells (EC) exposed to CoCl2 (1000 μM), P. gingivalis (MOI 100), and CoCl2 + P. gingivalis was evaluated through hypoxia detection fluorescence assay, antioxidant concentration colorimetric assay, and RTqPCR. Evaluation of M101 on EC proliferation was evaluated in an in vitro wound assay. In experimental periodontitis, periodontal wound healing and osteoclastic activity were compared among natural wound healing, placebo, and gels containing M101 (1  and 2 g/L) groups through histomorphometry and TRAP (tartrate-resistant acid phosphatase activity assay) assay respectively. The expression of HIF-1α, MMP-9, and NFκB in periodontal tissues was also evaluated through immunofluorescence studies.Results: M101 downregulated GLUT-1, GLUT-3, HIF-1α, and MMP-9 levels in EC exposed to CoCl2 , P. gingivalis, and CoCl2 + P. gingivalis (p < 0.05). Fluorescence and colorimetric analyses confirmed hypoxia reduction and antioxidant capacity improvement in such EC upon M101 treatment. Moreover, M101 improved significantly the in vitro wound closure. In vivo, the attachment level was significantly improved, and osteoclastic activity was reduced in mice treated with M101 gels compared to placebo and natural wound healing groups (p < 0.05). HIF-1α, MMP-9, and NFκB expression in periodontal tissues was reduced in M101 gels treated mice compared to the controls.Conclusion: M101 showed promise in resolving hypoxia and associated inflammation-mediated tissue degradation. Its potential in the clinical management of periodontitis must be further investigated. [ABSTRACT FROM AUTHOR]

A mass mortality was detected in the downstream section of one of the most extensive French populations of the endangered white-clawed crayfish, Austropotamobius pallipes, on June 26, 2013. This population occupied a 12 km stretch of the La Lucelle brook, with an estimated size of around 150 000 individuals. The presence of the crayfish plague pathogen was quickly diagnosed as the cause of the mortality, and monitoring was carried out to follow the spread of the disease from 15 July 2013 for one year. Results showed that after a fast spread between 15 and 25 July 2013 (upstream progression of mortality for about 4 km), the mortality front was limited to a stretch of a few hundred meters from August until December 2013. During winter, mortality was always observed, confirming that disease remained active. In April 2014, the mortality front was halted by a large dam in the brook (2 m high), 0.56 km from brook source. Two months later, 30 live crayfish were observed above the dam. On the 30 August 2014, no crayfish were found above the dam. Infected individuals analysed for microsatellite markers confirmed the Pacifastacus leniusculus strain of Aphanomyces astaci at the origin of this outbreak. Before the crayfish plague spread upstream of the large dam, a sample of 576 individuals was collected from upstream of the dam and translocated to another stream in the same French department. In July 2014, observations by night confirmed the presence of translocated white-clawed crayfish in the receiving brook.

γ-aminobutyric acid (GABA) acting on Cl−-permeable ionotropic type A (GABAA) receptors (GABAAR) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates. In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the construction of neural networks but GABA also acts as a potent trophic factor. In the present paper, we concentrate on brainstem and spinal motoneurons that are largely targeted by GABAergic interneurons, and we bring together data on the switch from excitatory to inhibitory effects of GABA, on the maturation of the GABAergic system and GABAAR subunits. We finally discuss the role of GABA and its GABAAR in immature hypoglossal motoneurons of the spastic (SPA) mouse, a model of human hyperekplexic syndrome.

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Allergy regroups numerous complex and various diseases classified as IgE-dependent or non–IgE-dependent hypersensitivities. IgEs are expressed as membrane and secreted forms by B cells and plasma cells, respectively. In IgE-mediated hypersensitivity, IgE secretion and binding to the high-affinity IgE receptor FcεRI on effector cells are responsible for the onset of allergic symptoms; in contrast, surface IgE expression as a B-cell receptor is barely detectable. Our aim was to test an innovative antisense approach to reducing IgE secretion. We designed an antisense oligonucleotide (ASO) targeting the polyadenylation signal of human secreted IgE to redirect IgE transcript polyadenylation from the secreted form to the membrane form. ASO treatments were performed on B cells from transgenic mice expressing humanized IgE (InEps mice), as well as on human primary B cells and myeloma cells. In vivo ASO delivery was tested by using an InEps mouse model. We demonstrated that treatment with a morpholino ASO targeting the secreted IgE polyadenylation signal drastically decreased IgE secretion and inversely increased membrane IgE mRNA expression. In addition, ASO treatment induced apoptosis of IgE-expressing U266 myeloma cells, and RNA sequencing revealed attenuation of their plasma cell phenotype. Remarkably, systemic administration of an ASO coupled with Pip6a as an arginine-rich cell-penetrating peptide decreased IgE secretion in vivo. Altogether, this ASO strategy could be an effective way to decrease IgE secretion and allergic symptoms in patients with IgE-dependent allergies, and it could also promote allergen tolerance through apoptosis of IgE+ antibody-secreting cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Osteoarthritis Research Society International (OARSI) Expert Consensus Guidelines recommend topical non-steroidal anti-inflammatory drugs as first-line medications for osteoarthritis (OA) knee pain, but several voluminous daily applications are required to achieve efficacy. There is a need to develop new and improved topical analgesics with a faster onset, longer duration of action, and the requirement to apply less gel. This trial investigated the safety and efficacy of a new 3.06% diclofenac gel (AMZ001) in subjects with knee OA. In total, 444 subjects (AMZ001 twice daily (BID) [ n = 121], AMZ001 once daily (QD) + placebo QD [ n = 121], placebo BID [ n = 121], or Voltaren 1% 4-times daily [ n = 81]) were enrolled. All except Voltaren 1% (single-blinded) were applied topically in a double-blind manner for a total of 4-weeks. The primary endpoint was the change from baseline to week 4 in the WOMAC pain sub-score in the target knee. Secondary and exploratory endpoints included additional efficacy measures (WOMAC total score, WOMAC function and stiffness sub-scores, WOMAC pain weight-bearing and non-weight-bearing sub-scores, ICOAP, chair-stand test, OMERACT-OARSI responder rate, PGA, WPAI, EQ-5D, rescue medication use, satisfaction questionnaire) and safety. Treatment with AMZ001 QD was effective at reducing WOMAC pain sub-scores vs placebo (estimated treatment difference [ETD]: −4.61 [95% confidence interval (CI): −9.09, −0.12]; p = 0.0440); however, BID application was not (ETD: −3.76 [95% CI: −8.21, 0.68]; p = 0.0969). For several secondary endpoints, changes from baseline to week 4 conferred nominally statistically significant improvements in favor of AMZ001 vs placebo, including PGA score (AMZ001 BID vs placebo, ETD: −0.61 [95% CI: −1.11, −0.11]; p = 0.0162; AMZ001 QD vs placebo, ETD: −0.63 [95% CI: −1.13, −0.13]; p = 0.0134), WPAI overall work impairment score (AMZ001 QD vs placebo, ETD: −10.44 [95% CI: −20.84, −0.04]; p = 0.0492), and EQ-5D VAS score (AMZ001 BID vs placebo, ETD: 4.70 [95% CI: 0.55, 8.85]; p = 0.0264). Post-hoc analysis excluding 11–14 subjects per group with pain scores that decreased between screening and baseline suggests a consistent effect of both AMZ001 QD (ETD: −5.84 [95% CI: −10.71, −0.97]; p = 0.0189) and BID (ETD: −5.35 [95% CI: −10.16, −0.54]; p = 0.0292) in reducing WOMAC pain sub-scores vs placebo. In general, treatment satisfaction was high, as measured by the satisfaction questionnaire. The frequency and incidence of adverse events (AEs) was greatest in the placebo group. Most AEs (>99%) were of mild or moderate severity. There were no serious AEs. There were no notable effects of any treatment on vital signs, ECGs, physical examination findings, or other laboratory assessments. Treatment with AMZ001 BID for 4 weeks improved WOMAC pain sub-scores; however, only QD application conferred nominally statistically significant improvements vs placebo. AMZ001 was generally well tolerated. [ABSTRACT FROM AUTHOR]