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BackgroundVaccines against SARS-CoV-2 have provided an invaluable resource in the fight against this infection. Given the current vaccine shortage, vaccination programs must prioritize their distribution to the most appropriate segments of the population. MethodsWe carried out a prospective cohort study with 63 health care workers (HCWs) from a public General Hospital. We compared antibody responses to two doses of BNT162b2 mRNA Covid-19 vaccine between HCWs with laboratory-confirmed SARS-CoV-2 infection before vaccination (experienced HCWs) and HCWs who were not previously infected (naive HCWs). ResultsSeven days after the first vaccine dose HCWs with previous infection experienced a 126 fold increase in antibody levels (GMC 26955 AU; 95% CI 18785-35125). However, in the HCW naive group the response was much lower and only 5 of them showed positive antibody levels (>50 AU). The HCWs with previous infection did not significantly increased their antibody levels after the second dose while there was a significant increase in the naive HCW group (16 fold; GMC 20227 AU; 95% CI: 15179-25275). Approximately two months after completing vaccination, the level of antibodies was much lower in naive HCWs (GMC 6595 AU vs. 25003 AU; p<0.001) ConclusionThe study shows that 10 months after the disease has passed, the immune system is capable of producing a rapid and powerful secondary antibody response after one single dose of the vaccine. This response reflects the persistence of immunological memory and it is independent of whether or not anti-SARS-CoV-2 antibodies are detected in blood. Besides, we found that the second dose does not improve the antibody response in individuals with previous Covid-19 infection. Nonetheless, two months later, the persistence of antibody levels is still higher in the experienced HCWs. These data suggest that immune memory remains for a long time in recovered individuals, and therefore, vaccination in this group could be postponed until immunization of the rest of the population is complete.

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Our knowledge about the gut microbiota of pigs is still scarce, despite the importance of these animals for biomedical research and agriculture. Here, we present a collection of cultured bacteria from the pig gut, including 110 species across 40 families and nine phyla. We provide taxonomic descriptions for 22 novel species and 16 genera. Meta-analysis of 16S rRNA amplicon sequence data and metagenome-assembled genomes reveal prevalent and pig-specific species within Lactobacillus, Streptococcus, Clostridium, Desulfovibrio, Enterococcus, Fusobacterium, and several new genera described in this study. Potentially interesting functions discovered in these organisms include a fucosyltransferase encoded in the genome of the novel species Clostridium porci, and prevalent gene clusters for biosynthesis of sactipeptide-like peptides. Many strains deconjugate primary bile acids in in vitro assays, and a Clostridium scindens strain produces secondary bile acids via dehydroxylation. In addition, cells of the novel species Bullifex porci are coccoidal or spherical under the culture conditions tested, in contrast with the usual helical shape of other members of the family Spirochaetaceae. The strain collection, called 'Pig intestinal bacterial collection' (PiBAC), is publicly available at www.dsmz.de/pibac and opens new avenues for functional studies of the pig gut microbiota.

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Primary progressive multiple sclerosis is a poorly understood disease entity with no specific prognostic biomarkers and scarce therapeutic options. We aimed to identify disease activity biomarkers in multiple sclerosis by performing an RNA sequencing approach in peripheral blood mononuclear cells from a discovery cohort of 44 untreated patients with multiple sclerosis belonging to different clinical forms and activity phases of the disease, and 12 healthy control subjects. A validation cohort of 58 patients with multiple sclerosis and 26 healthy control subjects was included in the study to replicate the RNA sequencing findings. The RNA sequencing revealed an interleukin 1 beta (IL1B) signature in patients with primary progressive multiple sclerosis. Subsequent immunophenotyping pointed to blood monocytes as responsible for the IL1B signature observed in this group of patients. Functional experiments at baseline measuring apoptosis-associated speck-like protein containing a CARD (ASC) speck formation showed that the NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome was overactive in monocytes from patients with primary progressive multiple sclerosis, and canonical NLRP3 inflammasome activation with a combination of ATP plus lipopolysaccharide was associated with increased IL1B production in this group of patients. Primary progressive multiple sclerosis patients with high IL1B gene expression levels in peripheral blood mononuclear cells progressed significantly faster compared to patients with low IL1B levels based on the time to reach an EDSS of 6.0 and the Multiple Sclerosis Severity Score. In agreement with peripheral blood findings, both NLRP3 and IL1B expression in brain tissue from patients with primary progressive multiple sclerosis was mainly restricted to cells of myeloid lineage. Treatment of mice with a specific NLRP3 inflammasome inhibitor attenuated established experimental autoimmune encephalomyelitis disease severity and improved CNS histopathology. NLRP3 inflammasome-specific inhibition was also effective in reducing axonal damage in a model of lipopolysaccharide-neuroinflammation using organotypic cerebellar cultures. Altogether, these results point to a role of IL1B and the NLRP3 inflammasome as prognostic biomarker and potential therapeutic target, respectively, in patients with primary progressive multiple sclerosis.

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Background and objective: Chronic relapsing inflammatory optic neuritis (CRION) is one of the more common phenotypes related to myelin oligodendrocyte glycoprotein antibodies (MOG-Abs). The absence of specific biomarkers makes distinguishing between CRION and relapsing inflammatory ON (RION) difficult. A recent work has suggested a widespread affectation of the central nervous system in CRION patients. In order to search for a potential CRION marker we have measured brain atrophy in a cohort of patients, stratified by phenotypes: CRION, RION, multiple sclerosis with a history of optic neuritis (MS-ON), and MOG-Abs status. Methods: A cross-sectional study was conducted in 31 patients (seven CRION, 11 RION, and 13 MS-ON). All patients were tested for MOG and aquaporin-4 antibodies (AQ4-Abs). Clinical data were collected. Brain atrophy was calculated by measuring the brain parenchyma fraction (BPF) with Neuroquant® software. Results: Four of seven CRION patients and one of 11 RION patients were positive for MOG-Abs (p = 0.046) and no MS-ON patients tested positive to MOG-Abs. All patients were negative to AQ4-Abs. The BPF was lower in patients with CRION than patients with RION (70.6 vs. 75.3%, p = 0.019) and similar to that in MS-ON patients. Conclusions: Brain atrophy in idiopathic inflammatory relapsing ON is present in patients with the CRION phenotype. Data from this study reflect that the optic nerve is a main target involved in these patients but not the only one. Our results should be further investigated in comprehensive and prospective studies.

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BACKGROUND: The first step in atherosclerosis formation is the ingurgitation of an oxidized low-density lipid (LDL) molecule by a macrophage which then turns into a foam cell within the vascular wall and initiates a cascade of inflammatory responses. Could it be that the potential cardioprotective effect observed in women receiving hormone replacement therapy (HRT) is modulated by estrogen's capacity to decrease LDL oxidation in the vascular wall and thus decrease atherosclerotic foam cells? MATERIALS AND METHODS: Thirty-four adult female Wistar rats were divided into three groups. All were double oophorectomized. After recovery, Group 1 received Estradiol Valerate subcutaneous (SC) (2.5 mg/kg/week), Group 2 Estradiol Valerate SC (2.5 mg/kg/week) + Progesterone SC (10 mg/kg/48 h), and Group 3 Placebo SC. After 10 weeks, all rats were sacrificed and a vascular dissection performed. Malondialdehyde (MDA) was measured directly on the vascular extract to determine lipid oxidative levels and HRTs' effect. Renal and hepatic tissue was also studied. Total antioxidant status (TAS) was measured to determine overall oxidative behavior. RESULTS: Vascular MDA levels for Group 1 = 80.80 (±16.8) µmol/ml/g, Group 2 = 107.69 (±24.9) µmol/ml/g, and Group 3 = 140.96 (±32.4) µmol/ml/g. ANOVA (P < 0.05), with a post hoc Bonferroni corrective t-test, showed that both Group 1 and 2 have statistically significant lower levels of MDA than Group 3. Renal tissue showed less oxidative damage in the HRT groups, while hepatic tissue showed an inverse behavior with less lipid oxidation in the placebo group. TAS decreased with oophorectomy in all groups but decreased less in both groups that received HRT compared to placebo (P < 0.05). CONCLUSION: HRT significantly reduces lipid oxidation directly in the arterial wall.

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OBJECTIVES: Glycated hemoglobin (HbA1c) is accepted as the most trusted marker for monitoring patients with diabetes mellitus. Ion-exchange high-performance liquid chromatography (HPLC) is one of the most widely used methods for HbA1c analysis. The presence of a hemoglobin variant can interfere with HbA1c quantification, requiring other analyses to clarify the results.Herein, we present two cases of Hb Le Lamentin, which, although they were the same variant, were thought to correspond to different hemoglobinopathies because of their percentages. DESIGN AND METHODS: Two male patients presented with an anomalous peak between HbA1c and HbA0 during a routine analysis of HbA1c using ion-exchange HPLC (Variant™ II Turbo).The hemoglobin variants were studied using capillary zone electrophoresis with the Sebia system, and the globin chains were analyzed by reverse-phase HPLC. A genetic analysis was performed using automated sequencing of the α2 and ß genes. RESULTS: In this work, we describe the first case of homozygous Hb Le Lamentin and the first double-heterozygous case of Hb Le Lamentin/Hb City of Hope. CONCLUSIONS: Although the presence of these variants does not lead to clinical anomalies, it also does not affect hematologic parameters. The variants have an impact on the determination of glycated hemoglobin levels using ion-exchange HPLC because the retention time interferes with the elution time of HbA1c, resulting in a falsely reduced value. Therefore, it is necessary to either recalculate the result or use another measurement method.

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