UPLC-MS profiling of low molecular weight phlorotannin polymers in Ascophyllum nodosum, Helvetia canaliculata and Fucus spiralis

Phlorotannins are a group of complex polymers, found in particular brown macroalgae, composed solely of the monomer phloroglucinol (1,3,5-trihydroxybenzene). Their structural complexity arises from the number of possible linkage positions between each monomer unit. This study aimed to profile the phlorotannin metabolite composition and the complexity of isomerisation present in brown macroalgae Ascophyllum nodosum, Pelvetia canaliculata and Fucus spiralis using UPLC-MS utilising a tandem quadrupole mass spectrometer. Phlorotannin-enriched fractions from water and aqueous ethanol extracts were analysed by UPLC-MS performed in multiple reaction monitoring mode to detect molecular ions consistent with the molecular weights of phlorotannins. Ascophyllum nodosum and P. canaliculata appeared to contain predominantly larger phlorotannins (degree of polymerisation (DP) of 6–13 monomers) compared to F. spiralis (DP of 4–6 monomers). This is the first report observing the complex chromatographic separation and metabolomic profiling of low molecular weight phlorotannins consisting of more than ten monomers. Extracted ion chromatograms, for each of the MRM transitions, for each species were analysed to profile the level of isomerisation for specific molecular weights of phlorotannins between 3 and 16 monomers. The level of phlorotannin isomerisation within the extracts of the individual macroalgal species differed to some degree, resulting in substantially different numbers of phlorotannin isomers for particular molecular weights. A similar UPLC-MS/MS separation procedure, as outlined in this study, may be used in the future as a means of screening the metabolite profile of macroalgal extracts, therefore, allowing extract consistency to be monitored for standardisation purposes

Glioblastoma Therapy with Cytotoxic Mesenchymal Stromal Cells Optimized by Bioluminescence Imaging of Tumor and Therapeutic Cell Response

Genetically modified adipose tissue derived mesenchymal stromal cells (hAMSCs) with tumor homing capacity have been proposed for localized therapy of chemo- and radiotherapy resistant glioblastomas. We demonstrate an effective procedure to optimize glioblastoma therapy based on the use of genetically modified hAMSCs and in vivo non invasive monitoring of tumor and therapeutic cells. Glioblastoma U87 cells expressing Photinus pyralis luciferase (Pluc) were implanted in combination with hAMSCs expressing a trifunctional Renilla reniformis luciferase-red fluorescent protein-thymidine kinase reporter in the brains of SCID mice that were subsequently treated with ganciclovir (GCV). The resulting optimized therapy was effective and monitoring of tumor cells by bioluminescence imaging (BLI) showed that after 49 days GCV treatment reduced significantly the hAMSC treated tumors; by a factor of 104 relative to controls. Using a Pluc reporter regulated by an endothelial specific promoter and in vivo BLI to image hAMSC differentiation we gained insight on the therapeutic mechanism. Implanted hAMSCs homed to tumor vessels, where they differentiated to endothelial cells. We propose that the tumor killing efficiency of genetically modified hAMSCs results from their association with the tumor vascular system and should be useful vehicles to deliver localized therapy to glioblastoma surgical borders following tumor resection

Obstetric–Neonatal Care during Birth and Postpartum in Symptomatic and Asymptomatic Women Infected with SARS-CoV-2: A Retrospective Multicenter Study

Data Availability Statement: Data are available upon reasonable request. All necessary data are supplied and available in the manuscript; however, the corresponding author will provide the dataset upon request. All data relevant to the study are included in the article.Copyright © 2022 by the authors. This study analyses the obstetric–neonatal outcomes of women in labour with symptomatic and asymptomatic COVID-19. A retrospective, multicenter, observational study was carried out between 1 March 2020 and 28 February 2021 in eight public hospitals in the Valencian community (Spain). The chi-squared test compared the obstetric–neonatal outcomes and general care for symptomatic and asymptomatic women. In total, 11,883 births were assisted in participating centers, with 10.9 per 1000 maternities (n = 130) infected with SARS-CoV-2. The 20.8% were symptomatic and had more complications both upon admission (p = 0.042) and during puerperium (p = 0.042), as well as transfer to the intensive care unit (ICU). The percentage of admission to the Neonatal Intensive Care Unit (NICU) was greater among offspring of symptomatic women compared to infants born of asymptomatic women (p < 0.001). Compared with asymptomatic women, those with symptoms underwent less labour companionship (p = 0.028), less early skin-to-skin contact (p = 0.029) and greater mother–infant separation (p = 0.005). The overall maternal mortality rate was 0.8%. No vertical transmission was recorded. In conclusion, symptomatic infected women are at increased risk of lack of labour companionship, mother–infant separation, and admission to the ICU, as well as to have preterm births and for NICU admissions.FISABIO grant number UGP-20-24

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

Objective: To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. Methods: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet =4 ACR-97 SLE criteria and disease onset <18 years old (jSLE), were retrospectively investigated for SI (defined as either the need for hospitalization with antibacterial therapy for a potentially fatal infection or death caused by the infection). Standardized SI rate was calculated per 100 patient years. Patients with and without SI were compared. Bivariate and multivariate logistic and Cox regression models were built to calculate associated factors to SI and relative risks. Results: A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and =6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2–4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. Conclusions: The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

Background Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Methods Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. Results 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). Conclusions CD4/CD8 > 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1)