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Fucoidan is a polymer of L-fucose and L-fucose-4-sulphate naturally found in marine sources that inhibits p-selectin, preventing neutrophil recruitment to the site of injury. Fucoidan is employed in many studies as a tool to investigate the contribution of neutrophils to pain, showing analgesic effects. We performed a systematic review and meta-analysis to quantify the analgesic effects of pretreatment with fucoidan reported in the available preclinical studies. In addition, we summarized the articles which have studied the therapeutic effects of fucoidan in pathological pain at preclinical and clinical levels. The results of this systematic review reveal that pretreatment with fucoidan is a powerful tool which reduces neutrophil infiltration by 70–90% at early time points. This meta-analysis showed that preventative treatment with fucoidan produced a significant pain reduction. In addition, several preclinical studies have observed that fucoidan treatment reduces the pain that is associated with various pathologies. Finally, fucoidan has also been tested in several clinical trials, with some degree of analgesic efficacy, but they were mostly small pilot studies. Considering all the above information, it can be concluded that fucoidan is not only a preclinical tool for studying the role of neutrophils in pain but also a promising therapeutic strategy for pain treatment.

The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.

The pharmacological treatment of cancer-related pain is unsatisfactory. Tetrodotoxin (TTX) has shown analgesia in preclinical models and clinical trials, but its clinical efficacy and safety have not been quantified. For this reason, our aim was to perform a systematic review and meta-analysis of the clinical evidence that was available. A systematic literature search was conducted in four electronic databases (Medline, Web of Science, Scopus, and ClinicalTrials.gov) up to 1 March 2023 in order to identify published clinical studies evaluating the efficacy and security of TTX in patients with cancer-related pain, including chemotherapy-induced neuropathic pain. Five articles were selected, three of which were randomized controlled trials (RCTs). The number of responders to the primary outcome (≥30% improvement in the mean pain intensity) and those suffering adverse events in the intervention and placebo groups were used to calculate effect sizes using the log odds ratio. The meta-analysis showed that TTX significantly increased the number of responders (mean = 0.68; 95% CI: 0.19–1.16, p = 0.0065) and the number of patients suffering non-severe adverse events (mean = 1.13; 95% CI: 0.31–1.95, p = 0.0068). However, TTX did not increase the risk of suffering serious adverse events (mean = 0.75; 95% CI: −0.43–1.93, p = 0.2154). In conclusion, TTX showed robust analgesic efficacy but also increased the risk of suffering non-severe adverse events. These results should be confirmed in further clinical trials with higher numbers of patients.

Seabirds drastically transform the environmental conditions of the sites where they establish their breeding colonies via soil, sediment, and water eutrophication (hereafter termed ornitheutrophication). Here, we report worldwide amounts of total nitrogen (N) and total phosphorus (P) excreted by seabirds using an inventory of global seabird populations applied to a bioenergetics model. We estimate these fluxes to be 591 Gg N y −1 and 99 Gg P y −1 , respectively, with the Antarctic and Southern coasts receiving the highest N and P inputs. We show that these inputs are of similar magnitude to others considered in global N and P cycles, with concentrations per unit of surface area in seabird colonies among the highest measured on the Earth’s surface. Finally, an important fraction of the total excreted N (72.5 Gg y −1 ) and P (21.8 Gg y −1 ) can be readily solubilized, increasing their short-term bioavailability in continental and coastal waters located near the seabird colonies. The global impact of seabird populations on nutrient cycles is poorly understood. Here, the authors use a bioenergetic model and a global seabird population inventory to estimate the amounts of nitrogen and phosphorus excreted by seabirds and estimate them to be 591 Gg N y −1 and 99 Gg P y −1 respectively.

Abstract First isolated in 1981, Mycoplasma genitalium is now well recognized as a frequent cause of urethritis and several other urogenital syndromes in both men and women. The cytoadhesins P110 (MgpC) and P140 (MgpB), located in the terminal organelle of the bacterium, mediate the establishment and persistence of M. genitalium infection in the reproductive tract tissues. This adhesion complex exposes a large extracellular domain, mediating bacterial adhesion to the anogenital tissue. The antigenic variation promoted by reciprocal recombination contribute to the efficient colonization of the urogenital environment and the immune evasion strategy of the bacterium. Although M. genitalium was traditionally detected in ano-genital samples, sexual transmission was not postulated until the early 2000s. Now, it is well accepted that M. genitalium can lead to a sexually transmitted infection. While vaginal sex may constitute the primary transmission route in terms of risk, anal intercourse in men who have sex with men is likely the most common cause of spread. Acknowledging the exquisite adaptation of the bacterium to diverse ecological niches in the human body, the unique features of the proteins P110 and P140 may influence transmission, dissemination and disease. Cytadhesins P110 and P140 are key for the pathogenesis and transmission of Mycoplasma genitalium infection

The mechanisms for neuropathic pain amelioration by sigma-1 receptor inhibition are not fully understood. We studied genome-wide transcriptomic changes (RNAseq) in the dorsal root ganglia (DRG) from wild-type and sigma-1 receptor knockout mice prior to and following Spared Nerve Injury (SNI). In wildtype mice, most of the transcriptomic changes following SNI are related to the immune function or neurotransmission. Immune function transcripts contain cytokines and markers for immune cells, including macrophages/monocytes and CD4 + T cells. Many of these immune transcripts were attenuated by sigma-1 knockout in response to SNI. Consistent with this we found, using flow cytometry, that sigma-1 knockout mice showed a reduction in macrophage/monocyte recruitment as well as an absence of CD4 + T cell recruitment in the DRG after nerve injury. Sigma-1 knockout mice showed a reduction of neuropathic (mechanical and cold) allodynia and spontaneous pain-like responses (licking of the injured paw) which accompany the decreased peripheral neuroinflammatory response after nerve injury. Treatment with maraviroc (a CCR5 antagonist which preferentially inhibits CD4 + T cells in the periphery) of neuropathic wild-type mice only partially replicated the sigma-1 knockout phenotype, as it did not alter cold allodynia but attenuated spontaneous pain-like responses and mechanical hypersensitivity. Therefore, modulation of peripheral CD4 + T cell activity might contribute to the amelioration of spontaneous pain and neuropathic tactile allodynia seen in the sigma-1 receptor knockout mice, but not to the effect on cold allodynia. We conclude that sigma-1 receptor inhibition decreases DRG neuroinflammation which might partially explain its anti-neuropathic effect. Graphical Abstract

Mycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on the N-terminal domain surfaces of P1 and P40/P90. Polyclonal antibodies generated against the mostly conserved C-terminal domain of P1 inhibited adhesion of M. pneumoniae , and serology assays with sera from infected patients were positive when tested against this C-terminal domain. P40/P90 also showed strong reactivity against human infected sera. The architectural elements determined for P1 and P40/P90 open new possibilities in vaccine development against M. pneumoniae infections. Adhesion of the human pathogen Mycoplasma pneumoniae to pulmonary epithelial cells is mediated by a transmembrane complex composed of proteins P1 and P40/P90. Here, the authors present the structures of M. pneumoniae P1 and P40/P90, show that P40/P90 binds sialylated oligosaccharides and have also determined the crystal structures of P40/P90 complexes with 3’-Sialyllactose and 6’-Sialyllactose, which provide insights into the mechanisms of adhesion and gliding on host cell surfaces.

Objective We aimed to estimate autumn 2023 COVID‐19 vaccine effectiveness (CVE) in preventing hospitalizations due to COVID‐19 until September 2024. Methods We performed a test‐negative case–control study nested in the cohort of adults aged ≥ 45 years with indication of autumn 2023 COVID‐19 vaccination in Navarre, Spain. The study included patients hospitalized for severe acute respiratory infection (SARI) and tested by polymerase chain reaction between October 2023 and September 2024. The COVID‐19 vaccination statuses in the current and previous seasons were compared between confirmed COVID‐19 cases and test‐negative controls. CVE was estimated as (1 − adjusted odds ratio) × 100. Results Of 4051 SARI hospitalized patients included in the study, 474 (12%) were confirmed for COVID‐19. CVE to prevent COVID‐19 hospitalizations was 32% (95% confidence interval [CI], 11%–48%) on average for the year and 38% (95% CI, 17%–54%) among people aged ≥ 65 years. However, estimates for current‐season vaccination were 51% (95% CI, 30%–66%), 50% (95% CI, 16%–70%), and 0% (95% CI, −42% to 30%) for 7 to 89, 90 to 179, and ≥ 180 days between vaccination and COVID‐19 diagnosis, respectively. The residual effect of previous‐season vaccination was not statistically significant (14%; 95% CI, −20% to 39%). CVE was moderate in preventing COVID‐19 hospitalizations between October 2023 and March 2024 (50%; 95% CI, 28%–65%), and null between April and September 2024 (6%; 95% CI, −41% to 38%). The vaccine averted 19% of COVID‐19 hospitalizations. On average, 963 doses of vaccine were necessary to prevent one COVID‐19 hospitalization. Conclusions CVE was moderate in preventing COVID‐19 hospitalizations during the 2023–2024 season, but decreased 6 months after vaccination.