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Neuropathic itch is a type of chronic pruritus resulting from neural dysfunction along the afferent pathway. It is often accompanied by abnormal sensations such as paresthesia, hyperesthesia, or hypoesthesia. This condition, which may involve motor or autonomic neural damage, significantly impacts patients' quality of life, causing severe itch and associated comorbidities such as depression, disrupted sleep, and social strain. Neuropathic itch accounts for 8% of chronic pruritus cases, though this may be underestimated. This comprehensive review focuses on nerve impingement as the primary pathophysiological mechanism for various forms of neuropathic itch including brachioradial pruritus (BRP), notalgia paresthetica (NP), and anogenital itch. BRP, often seen in middle-aged white women, manifests as pruritus in the dorsolateral forearms typically exacerbated by ultraviolet (UV) exposure and related to cervical spine pathology. NP, prevalent in middle-aged women, presents as pruritus in the upper back due to thoracic spine nerve compression. Anogenital pruritus, affecting 1-5% of adults, is often linked to lumbosacral spine issues after ruling out dermatologic conditions such as lichen sclerosus or lichen simplex chronicus. The pathophysiology of neuropathic itch involves both peripheral and central mechanisms, with nerve damage being a key factor. Diagnosis requires a thorough history, physical examination, and potentially imaging studies. Topical agents such as menthol, capsaicin, and lidocaine are used for mild cases, while systemic medications such as gabapentin, pregabalin, and antidepressants are prescribed for moderate to severe cases; however, no US Food and Drug Administration (FDA)-approved therapies currently exist specifically for neuropathic itch. Understanding the underlying neural dysfunction and appropriate therapeutic strategies is crucial for managing neuropathic itch effectively.

First-generation histamine 1 antihistamines have been reported to exhibit cardiac side efects including dose-dependent sinus tachycardia, corrected QT interval prolongation, prolonged atrial refractive period, and refex tachycardia [4]. [...]generation antihistamine safety has been documented with increased dosing of up to four-fold in the treatment of CSU [7]. [...]our study demonstrated that patients with CSU may be at an increased risk for comorbid cardiac conditions.

Neuropathic itch is a type of chronic pruritus resulting from neural dysfunction along the afferent pathway. It is often accompanied by abnormal sensations such as paresthesia, hyperesthesia, or hypoesthesia. This condition, which may involve motor or autonomic neural damage, significantly impacts patients’ quality of life, causing severe itch and associated comorbidities such as depression, disrupted sleep, and social strain. Neuropathic itch accounts for 8% of chronic pruritus cases, though this may be underestimated. This comprehensive review focuses on nerve impingement as the primary pathophysiological mechanism for various forms of neuropathic itch including brachioradial pruritus (BRP), notalgia paresthetica (NP), and anogenital itch. BRP, often seen in middle-aged white women, manifests as pruritus in the dorsolateral forearms typically exacerbated by ultraviolet (UV) exposure and related to cervical spine pathology. NP, prevalent in middle-aged women, presents as pruritus in the upper back due to thoracic spine nerve compression. Anogenital pruritus, affecting 1–5% of adults, is often linked to lumbosacral spine issues after ruling out dermatologic conditions such as lichen sclerosus or lichen simplex chronicus. The pathophysiology of neuropathic itch involves both peripheral and central mechanisms, with nerve damage being a key factor. Diagnosis requires a thorough history, physical examination, and potentially imaging studies. Topical agents such as menthol, capsaicin, and lidocaine are used for mild cases, while systemic medications such as gabapentin, pregabalin, and antidepressants are prescribed for moderate to severe cases; however, no US Food and Drug Administration (FDA)-approved therapies currently exist specifically for neuropathic itch. Understanding the underlying neural dysfunction and appropriate therapeutic strategies is crucial for managing neuropathic itch effectively.

The microbiome of the female reproductive tract has implications for women’s reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant women of African, Hispanic or European ancestry case-matched for race, gestational age and household income; and a longitudinally sampled cohort of 90 pregnant women of African or non-African ancestry. In these women, the vaginal microbiome shifted during pregnancy toward Lactobacillus-dominated profiles at the expense of taxa often associated with vaginal dysbiosis. The shifts occurred early in pregnancy, followed predictable patterns, were associated with simplification of the metabolic capacity of the microbiome and were significant only in women of African or Hispanic ancestry. Both genomic and environmental factors are likely contributors to these trends, with socioeconomic status as a likely environmental influence.Ancestry and socioeconomic factors influence predictable changes in the vaginal microbiome that occur early in pregnancy in women who experience normal term birth.

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes ‘omics’ data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.As part of the second phase of Human Microbiome Project, the Multi-Omic Microbiome Study: Pregnancy Initiative presents a community resource to help better understand how microbiome and host profiles change throughout pregnancy as well as to identify new opportunities for assessment of the risk of preterm birth.

Prostate cancer is the second leading cause of male cancer death in the U.S. Current immune checkpoint inhibitor-based immunotherapies have improved survival for many malignancies; however, they have failed to prolong survival for prostate cancer. Siglecs (sialic acid-binding immunoglobulin-like lectins) are expressed on immune cells and regulate their function. Siglec-7 and Siglec-9 contribute to immune evasion in cancer by interacting with sialic acid-containing glycoprotein ligands on cancer cells. However, the role of Siglec-7/9 receptors and their ligands in prostate cancer remains poorly understood. Here, we find that Siglec-7 and Siglec-9 are associated with poor prognosis in patients with prostate cancer and are highly expressed in myeloid cells, including macrophages, in prostate tumor tissues. Siglec-7 and -9 ligands were expressed in prostate cancer cells and human prostate tumor tissues. Blocking the interactions between Siglec-7/9 and sialic acids inhibited prostate cancer xenograft growth and increased immune cell infiltration in humanized mice in vivo. Using a CRISPRi screen and mass spectrometry, we identified CD59 as a candidate Siglec-9 ligand in prostate cancer. The identification of Siglec-7 and -9 as potential therapeutic targets, including the CD59/Siglec-9 axis, opens up opportunities for immune-based interventions in prostate cancer.

Fluxes of sea spray aerosols were measured with the eddy covariance technique from the Penlee Point Atmospheric Observatory (PPAO) on the southwest coast of the United Kingdom over several months from 2015 to 2017. Two different fast-responding aerosol instruments were employed: an ultra-fine condensation particle counter (CPC) that detects aerosols with a radius above ca. 1.5 nm and a compact lightweight aerosol spectrometer probe (CLASP) that provides a size distribution between ca. 0.1 and 6 µm. The measured sea spray emission fluxes essentially all originated from the shallow waters upwind, rather than from the surf zone/shore break. Fluxes from the CPC and from the CLASP (integrated over all sizes) were generally comparable, implying a reasonable closure in the aerosol number flux. Compared to most previous observations over the open ocean, at the same wind speed the mean sea spray number fluxes at PPAO are much greater. Significant wave height and wave Reynolds numbers explain more variability in sea spray fluxes than wind speed does, implying that enhanced wave breaking resulting from shoaling in shallow coastal waters is a dominant control on sea spray emission. Comparisons between two different wind sectors (open water vs. fetch-limited Plymouth Sound) and between two sets of sea states (growing vs. falling seas) further confirm the importance of wave characteristics on sea spray fluxes. These results suggest that spatial variability in wave characteristics need to be taken into account in predictions of coastal sea spray productions and also aerosol loading.

Two consecutive cruises in the Weddell Sea, Antarctica, in winter 2013 provided the first direct observations of sea salt aerosol (SSA) production from blowing snow above sea ice, thereby validating a model hypothesis to account for winter time SSA maxima in the Antarctic. Blowing or drifting snow often leads to increases in SSA during and after storms. For the first time it is shown that snow on sea ice is depleted in sulfate relative to sodium with respect to seawater. Similar depletion in bulk aerosol sized ∼0.3–6 µm above sea ice provided the evidence that most sea salt originated from snow on sea ice and not the open ocean or leads, e.g. >90 % during the 8 June to 12 August 2013 period. A temporally very close association of snow and aerosol particle dynamics together with the long distance to the nearest open ocean further supports SSA originating from a local source. A mass budget estimate shows that snow on sea ice contains even at low salinity (<0.1 psu) more than enough sea salt to account for observed increases in atmospheric SSA during storms if released by sublimation. Furthermore, snow on sea ice and blowing snow showed no or small depletion of bromide relative to sodium with respect to seawater, whereas aerosol was enriched at 2 m and depleted at 29 m, suggesting that significant bromine loss takes place in the aerosol phase further aloft and that SSA from blowing snow is a source of atmospheric reactive bromine, an important ozone sink, even during winter darkness. The relative increase in aerosol concentrations with wind speed was much larger above sea ice than above the open ocean, highlighting the importance of a sea ice source in winter and early spring for the aerosol burden above sea ice. Comparison of absolute increases in aerosol concentrations during storms suggests that to a first order corresponding aerosol fluxes above sea ice can rival those above the open ocean depending on particle size. Evaluation of the current model for SSA production from blowing snow showed that the parameterizations used can generally be applied to snow on sea ice. Snow salinity, a sensitive model parameter, depends to a first order on snowpack depth and therefore was higher above first-year sea ice (FYI) than above multi-year sea ice (MYI). Shifts in the ratio of FYI and MYI over time are therefore expected to change the seasonal SSA source flux and contribute to the variability of SSA in ice cores, which represents both an opportunity and a challenge for the quantitative interpretation of sea salt in ice cores as a proxy for sea ice.

IntroductionUnderstanding the effectiveness and durability of protection against SARS-CoV-2 infection conferred by previous infection and COVID-19 is essential to inform ongoing management of the pandemic. This study aims to determine whether prior SARS-CoV-2 infection or COVID-19 vaccination in healthcare workers protects against future infection.Methods and analysisThis is a prospective cohort study design in staff members working in hospitals in the UK. At enrolment, participants are allocated into cohorts, positive or naïve, dependent on their prior SARS-CoV-2 infection status, as measured by standardised SARS-CoV-2 antibody testing on all baseline serum samples and previous SARS-CoV-2 test results. Participants undergo monthly antibody testing and fortnightly viral RNA testing during follow-up and based on these results may move between cohorts. Any results from testing undertaken for other reasons (eg, symptoms, contact tracing) or prior to study entry will also be captured. Individuals complete enrolment and fortnightly questionnaires on exposures, symptoms and vaccination. Follow-up is 12 months from study entry, with an option to extend follow-up to 24 months.The primary outcome of interest is infection with SARS-CoV-2 after previous SARS-CoV-2 infection or COVID-19 vaccination during the study period. Secondary outcomes include incidence and prevalence (both RNA and antibody) of SARS-CoV-2, viral genomics, viral culture, symptom history and antibody/neutralising antibody titres.Ethics and disseminationThe study was approved by the Berkshire Research Ethics Committee, Health Research Authority (IRAS ID 284460, REC reference 20/SC/0230) on 22 May 2020; the vaccine amendment was approved on 12 January 2021. Participants gave informed consent before taking part in the study.Regular reports to national and international expert advisory groups and peer-reviewed publications ensure timely dissemination of findings to inform decision making.Trial registration numberISRCTN11041050.

Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs) and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors”) can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.