Antimicrobial drug (AMD) use for bovine respiratory disease (BRD) continues to be concerning for development of antimicrobial resistance (AMR) in respiratory and enteric bacteria of cattle. This study aimed to provide data regarding AMR in respiratory isolates, and identify relationships between respiratory and enteric AMD susceptibility, in weaned dairy heifers. A cross-sectional study was performed between June of 2019 and February 2020, on 6 calf rearing facilities in California. Deep nasopharyngeal and rectal swabs were collected from 341 weaned heifers and submitted for selective bacterial culture and AMR testing. Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni were selectively isolated from respiratory samples; Escherichia coli and Enterococcus spp. were selectively isolated from rectal swabs. Minimum inhibitory concentrations (MIC) were determined for selected isolates against 19 AMD. The proportion of resistant isolates was calculated using Clinical Laboratory Standards Institute (respiratory) or USDA NARMS (enteric) breakpoints; when no applicable breakpoint was available, the distribution of MIC was described and compared. Association between AMR in a calf's respiratory isolate and a higher or lower MIC of the matched enteric isolates was determined. More than 50% of P. multocida isolates were resistant to each of 7 AMD commonly used to treat BRD (florfenicol, gamithromycin, tildipirosin, tilmicosin, danofloxacin, enrofloxacin and tetracycline). Resistance in respiratory isolates was only associated with higher matched enteric MIC for gamithromycin and tulathromycin. Multidrug resistance was reported in >70% of P. multocida and M. haemolytica isolates. Antimicrobial resistance, including multidrug resistance, in respiratory isolates appears to be widespread in weaned dairy heifers; this finding has not previously been reported and raises concern for the future efficacy of AMD used to treat respiratory diseases in weaned dairy heifers. Enteric bacterial MIC appear to have limited direct association with respiratory isolate AMR classification.

OBJECTIVES: To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS).

METHODS: By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression.

RESULTS: There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase).

CONCLUSIONS: The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.

Since ancient times, litchi has been well recognized as a functional food for the management of various ailments. Many bioactives, including flavanoids, anthocyanins, phenolics, sesquiterpenes, triterpenes, and lignans, have been identified from litchi with a myriad of biological properties both and . In spite of the extensive research progress, systemic reviews regarding the bioactives of litchi are rather scarce. Therefore, it is crucial to comprehensively analyze the pharmacological activities and the structure-activity relationships of the abundant bioactives of litchi. Besides, more and more studies have focused on litchi preservation and development of its by-products, which is significant for enhancing the economic value of litchi. Based on the analysis of published articles and patents, this review aims to reveal the development trends of litchi in the healthcare field by providing a systematic summary of the pharmacological activities of its extracts, its phytochemical composition, and the nutritional and potential health benefits of litchi seed, pulp and pericarp with structure-activity relationship analysis. In addition, its by-products also exhibited promising development potential in the field of material science and environmental protection. Furthermore, this study also provides an overview of the strategies of the postharvest storage and processing of litchi.

The rapid transmission of SARS-CoV-2 in the USA and worldwide necessitates the development of multiple vaccines to combat the COVID-19 global pandemic. Previously, we showed that a particulate adjuvant system, quil-A-loaded chitosan (QAC) nanoparticles, can elicit robust immunity combined with plasmid vaccines when used against avian coronavirus. Here, we report on the immune responses elicited by mucosal homologous plasmid and a heterologous immunization strategy using a plasmid vaccine and a Modified Vaccinia Ankara (MVA) expressing SARS-CoV-2 spike (S) and nucleocapsid (N) antigens. Only the heterologous intranasal immunization strategy elicited neutralizing antibodies against SARS-CoV-2 in serum and bronchoalveolar lavage of mice, suggesting a protective vaccine. The same prime/boost strategy led to the induction of type 1 and type 17 T-cell responses and polyfunctional T-cells expressing multiple type 1 cytokines (e.g., IFN-γ, TNFα, IL-2) in the lungs and spleens of vaccinated mice. In contrast, the plasmid homologous vaccine strategy led to the induction of local mono and polyfunctional T-cells secreting IFN-γ. Outcomes of this study support the potential of QAC-nano vaccines to elicit significant mucosal immune responses against respiratory coronaviruses.

PDZ domains are one of the most abundant protein domains in eukaryotes and are frequently found on junction-localized scaffold proteins. Various signaling molecules bind to PDZ proteins via PDZ-binding motifs (PBM) and fine-tune cellular signaling. However, how such interaction affects protein function is difficult to predict and must be solved empirically. Here we describe a long isoform of the guanine nucleotide exchange factor GIV/Girdin (CCDC88A) that we named GIV-L, which is conserved throughout evolution, from invertebrates to vertebrates, and contains a PBM. Unlike GIV, which lacks PBM and is cytosolic, GIV-L localizes onto cell junctions and has a PDZ interactome (as shown through annotating Human Cell Map and BioID-proximity labeling studies), which impacts GIV-L's ability to bind and activate trimeric G-protein, Gαi, through its guanine-nucleotide exchange modulator (GEM) module. This GEM module is found exclusively in vertebrates. We propose that the two functional modules in GIV may have evolved sequentially: the ability to bind PDZ proteins via the PBM evolved earlier in invertebrates, whereas G-protein binding and activation may have evolved later only among vertebrates. Phenotypic studies in Caco-2 cells revealed that GIV and GIV-L may have antagonistic effects on cell growth, proliferation (cell cycle), and survival. Immunohistochemical analysis in human colon tissues showed that GIV expression increases with a concomitant decrease in GIV-L during cancer initiation. Taken together, these findings reveal how regulation in GIV/CCDC88A transcript helps to achieve protein modularity, which allows the protein to play opposing roles either as a tumor suppressor (GIV-L) or as an oncogene (GIV).

BACKGROUND: The World Health Organization (WHO) set a goal to eliminate hepatitis C (HCV) infection globally by 2030, with specific targets to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to drive liver disease progression and offset the beneficial impact of DAAs on end-stage liver disease and hepatocellular carcinoma (HCC). In particular, the decrease in HCV prevalence has been countered by a marked increase in the prevalence of metabolic-associated fatty liver disease (MAFLD).

AIMS: To review the potential interaction of HCV and MAFLD.

METHODS: We have reviewed the literature relating to an arrange of interaction of HCV, metabolic dysfunction and MAFLD.

RESULTS: In this viewpoint, international experts suggest a holistic and multidisciplinary approach for the management of the growing number of treated HCV patients who achieved SVR, taking into consideration the overlooked impact of MAFLD for reducing morbidity and mortality in people who have had HCV.

CONCLUSIONS: This will strengthen and improve the continuum of care cascade for patients with liver disease(s) and holds the potential to alleviate the cost burden of disease; and increase quality of life for patients following DAAs treatment.

Mayaro virus (MAYV) is an emerging mosquito-transmitted virus that belongs to the genus

BACKGROUND: To evaluate the changes in the mean macular intercapillary area (ICA) from sequential enface optical coherence tomography angiography (OCTA) images following intravitreal anti-vascular endothelial growth factor (VEGF) therapy in initially treatment-naïve eyes with diabetic macular oedema (DME).

METHODS: In this multicentre retrospective study, 6 × 6 and 3 × 3 mm customised, total retinal projection enface OCTA images were collected and processed for quantitative assessment of ICA by a customised MATLAB software. Measurements were done in concentric regions centred on the fovea-with the exclusion of foveal avascular zone (FAZ)-in 0.5 mm diameter increments as well as within the intervening rings.

RESULTS: In this study, 6 × 6 mm OCTA images from 46 eyes of 29 patients, and 3 × 3 mm OCTA images from 23 eyes of 15 patients were included. There was no significant change in mean ICA after treatment in either scan size or in any measurement regions (all p > 0.05). Multivariate analysis revealed that baseline BCVA was significantly correlated with the visual outcome (p = 0.039). Additionally, after correction for age, baseline central retinal thickness (CRT), baseline BCVA, and retinopathy severity, mean ICA in the 1.5 mm circle was found to be a significant predictor of post treatment CRT, (p = 0.006).

CONCLUSIONS: Absence of significant change in mean ICA after a minimum of three intravitreal anti-VEGF injections, may indicate that, in the short term, anti-VEGF injections neither impair nor improve macular perfusion in DME. Baseline BCVA was found to be a robust predictor of functional outcome, while inner mean ICA was a significant predictor for macular thickness outcomes.