Characteristics and clinical outcome in 312 patients with moderate to severe pneumonia due to SARS-COV-2 and hyperinflammation treated with anakinra and corticosteroids: A retrospective cohort study

S1 File. Statistical analysis of all assessed variables in our cohort and among different treat- ment groups. (PDF) file:///C:/Users/Usuario1/Downloads/journal.pone.0283529.s001-1.pdfObjectiveTo assess the clinical outcome (death and/or Intensive Care Unit (ICU) admission) based on the time from hospital admission to the administration of anakinra and the possible usefulness of a "simplified" SCOPE score to stratify the risk of worse prognosis in our cohort of patients with moderate/severe SARS-CoV-2 pneumonia, both vaccinated and unvaccinated, that received anakinra and corticosteroids. In addition, the clinical, analytical, and imaging characteristics of patients at admission are described. MethodsRetrospective cohort study of 312 patients admitted to Hospital Clinico San Cecilio in Granada for moderate/severe pneumonia caused by SARS-CoV-2 that received anakinra and corticosteroids between March 2020 and January 2022. Clinical and analytical data were collected as well as the patient outcome at 30 and 60 days after admission. Three treatment groups were established according to the time from hospital admission to administration of anakinra: early (1st-2nd day), intermediate (3rd-5th day), and late (after the 5th day). ResultsThe median age was 67.4 years (IQR 22-97 years) and 204 (65.4%) were male. The most common comorbidity was hypertension (58%). The median time from the start of symptoms to anakinra administration was 6 days (IQR 5-10) and the SaFi (SaO(2)/FiO(2)) was 228 (IQR 71-471). The cure rate was higher in the early-onset anakinra group versus the late-onset group (73% vs 56.6%). The latter had a higher percentage of deaths (27.4%) and a greater number of patients remained hospitalized for a month (16%). On admission, the patients had elevated C-reactive protein (CRP), ferritin, and D-dimer values and decreased total lymphocytes. Analytical improvement was observed at both 72 hours and one month after treatment. 42 (13.5%) required ICU admission, and 23 (7.3%) orotracheal intubation. At 60 days, 221 (70.8%) were discharged, 87 (27.8%) had died and 4 (1.4%) remained hospitalized. The mean dose of anakinra was 1000 mg (100-2600 mg) with differences found between the dose administered and the clinical outcome. There were no differences in the primary outcome based on vaccination.A simplified SCOPE score at the start of anakinra administration was lower in patients with better clinical evolution. ConclusionsEarly treatment with anakinra and corticosteroids was associated with a better outcome regardless of vaccination status. A simplified SCOPE was found to be a good prognostic tool.SOB

Fortification of Fermented Camel Milk with Salvia officinalis L. or Mentha piperita Leaves Powder and Its Biological Effects on Diabetic Rats

Researchers Supporting Project number (RSPD2023R655), King Saud University, Riyadh, Saudi Arabia.Supplementary Materials: The following supporting information can be downloaded from: https://www.mdpi.com/article/10.3390/molecules28155749/s1The incorporation of fermented camel milk with natural additives possesses numerous benefits for the treatment of various pathological and metabolic conditions. The present study investigated the impact of fortification of fermented camel milk with sage or mint leaves powder (1 and 1.5%, respectively) on glucose and insulin levels, lipid profile, and liver and kidney functions in alloxan-induced diabetic rats. The gross chemical composition of sage and peppermint leaves powder was studied. The chemical composition of sage and mint extracts was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS) of sage and mint extracts. Furthermore, a total of forty-two adult normal male albino rats were included in this study, whereas one group was kept as the healthy control group (n = 6 rats) and diabetes was induced in the remaining animals (n = 36 rats) using alloxan injection (150 mg/kg of body weight). Among diabetic rats groups, a control group (n = 6 rats) was kept as the diabetic control group whereas the other 5 groups (6 rats per group) of diabetic rats were fed fermented camel milk (FCM) or fermented camel milk fortified with 1 and 1.5% of sage or mint leaves powder. Interestingly, the oral administration of fermented camel milk fortified with sage or mint leaves powder, at both concentrations, caused a significant decrease in blood glucose level and lipid profile, and an increase in insulin level compared to the diabetic control and FCM groups. Among others, the best results were observed in the group of animals that received fermented camel milk fortified with 1.5% sage powder. In addition, the results revealed that the fermented camel milk fortified with sage or mint leaves powder improved the liver and kidney functions of diabetic rats. Our study concluded that the use of sage and mint leaves powder (at a ratio of 1.5%) with fermented camel milk produces functional food products with anti-diabetic activity.Researchers Supporting Project, King Saud University, Riyadh, Saudi Arabia RSPD2023R655European Union-NextGenerationE

Dose-Dependent Effect of Melatonin on BAT Thermogenesis in Zücker Diabetic Fatty Rat: Future Clinical Implications for Obesity

Experimental data have revealed that melatonin at high doses reduced obesity and improved metabolic outcomes in experimental models of obesity, mainly by enhancing brown adipose tissue (BAT) thermogenesis. A potential dose-response relationship has yet to be performed to translate these promising findings into potential clinical therapy. This study aimed to assess the effects of different doses of melatonin on interscapular BAT (iBAT) thermogenic capacity in Zücker diabetic fatty (ZDF) rats. At 6 wk of age, male ZDF rats were divided into four groups (n = 4 per group): control and those treated with different doses of melatonin (0.1, 1, and 10 mg/kg of body weight) in their drinking water for 6 wk. Body weight (BW) was significantly decreased at doses of 1 and 10 mg/kg of melatonin, but not at 0.1 mg/kg compared with the control, with a similar rate of BW decrease being reached at the dose of 1 mg/kg (by ~11%) and 10 mg/kg (by ~12%). This effect was associated with a dose-dependent increase in the thermal response to the baseline condition or acute cold challenge in the interscapular area measurable by infrared thermography, with the highest thermal response being recorded at the 10 mg/kg dose. Upon histology, melatonin treatment markedly restored the typical brownish appearance of the tissue and promoted a shift in size distribution toward smaller adipocytes in a dose-dependent fashion, with the most pronounced brownish phenotype being observed at 10 mg/kg of melatonin. As a hallmark of thermogenesis, the protein level of uncoupled protein 1 (UCP1) from immunofluorescence and Western blot analysis increased significantly and dose-dependently at all three doses of melatonin, reaching the highest level at the dose of 10 mg/kg. Likewise, all three doses of melatonin modulated iBAT mitochondrial dynamics by increasing protein expression of the optic atrophy protein type 1 (OPA1) fusion marker and decreasing that of the dynamin-related protein1 (DRP1) fission marker, again dose-dependently, with the highest and lowest expression levels, respectively, being reached at the 10 mg/kg dose. These findings highlight for the first time the relevance of the dose-dependency of melatonin toward BW control and BAT thermogenic activation, which may have potential therapeutic implications for the treatment of obesity. To clinically apply the potential therapeutic of melatonin for obesity, we consider that the effective animal doses that should be extrapolated to obese individuals may be within the dose range of 1 to 10 mg/kg.Ministrio de Ciencia e Innovacion (Spain) SAF2016-79794-REuropean CommissionUniversity of Granada & FEDER Andalucia-UGR 2020 B-CTS-102-UGR2

Melatonin Improves Skeletal Muscle Structure and Oxidative Phenotype by Regulating Mitochondrial Dynamics and Autophagy in Zücker Diabetic Fatty Rat

Obesity-induced skeletal muscle (SKM) inflexibility is closely linked to mitochondrial dysfunction. The present study aimed to evaluate the effects of melatonin on the red vastus lateralis (RVL) muscle in obese rat models at the molecular and morphological levels. Five-week-old male Zücker diabetic fatty (ZDF) rats and their age-matched lean littermates (ZL) were orally treated either with melatonin (10 mg/kg body weight (BW)/24 h) (M–ZDF and M–ZL) or non-treated (control) (C–ZDF and C–ZL) for 12 weeks. Western blot analysis showed that mitochondrial fission, fusion, and autophagy were altered in the C-ZDF group, accompanied by reduced SIRT1 levels. Furthermore, C-ZDF rats exhibited depleted ATP production and nitro-oxidative stress, as indicated by increased nitrites levels and reduced SOD activity. Western blotting of MyH isoforms demonstrated a significant decrease in both slow and fast oxidative fiber-specific markers expression in the C-ZDF group, concomitant with an increase in the fast glycolytic fiber markers. At the tissue level, marked fiber atrophy, less oxidative fibers, and excessive lipid deposition were noted in the C-ZDF group. Interestingly, melatonin treatment partially restored mitochondrial fission/fusion imbalance in the RVL muscle by enhancing the expression of fission (Fis1 and DRP1) markers and decreasing that of fusion (OPA1 and Mfn2) markers. It was also found to restore autophagy, as indicated by increased p62 protein level and LC3BII/I ratio. In addition, melatonin treatment increased SIRT1 protein level, mitochondrial ATP production, and SOD activity and decreased nitrites production. These effects were associated with enhanced oxidative phenotype, as evidenced by amplified oxidative fiber-specific markers expression, histochemical reaction for NADH enzyme, and muscular lipid content. In this study, we showed that melatonin might have potential therapeutic implications for obesity-induced SKM metabolic inflexibility among patients with obesity and T2DMPID2021-125900OB-I00 from the Ministerio de Ciencia e Innovación (Spain)European Regional Development Fund (ERDF)B-CTS102-UGR from European Regional Development Fund (ERDF

Association of 25-hydroxyvitamin D with Metabolic Syndrome in Patients with Psoriasis: A Case-control Study

Vitamin D deficiency is associated with higher cardiovascular risk and metabolic syndrome (MeS) criteria. The main objective of this study was to analyse the association of 25-hydroxyvitamin D (25-OHD) serum levels with MeS (National Cholesterol Education Program Adult Treatment Panel-III criteria) in 46 Spanish patients with psoriasis, but without arthritis and systemic treatment, and 46 control subjects, matched by sex and age. The patients with psoriasis showed significantly lower level of 25-OHD than controls (30.5 vs. 38.3 ng/ml; p =0.0001). Patients with MeS had significantly lower serum levels of 25-OHD than those without MeS (24.1 +/- 7.5 vs. 32.8 +/- 8.9,p =0.007), and a negative correlation was found between 25-OHD and waist circumference, diastolic blood pressure, fasting glucose, and triglyceridaemia. In the control group no significant correlation between 25-OHD and MeS was found. Although the sample was small, our results suggest a potential protective role for 25-OHD in the metabolic profile of patients with psoriasis without arthritis

Valoración del locus DQ en pacientes con artritis reumatoide : correlación clínico-terapéutica

Reducción altaLa definición del locus dq en la 9 Reunión Internacional de Histocompatibilidad de 1.984 y su posterior desarrollo en la ultima celebrada en 1.987, nos indujo a intentar objetivar el papel que podrían jugar estos antígenos en la artritis reumatoide (ar) y en la génesis de la toxicidad aurica. Para ello utilizamos un grupo control de 274 sujetos sanos para la tipificación de los antígenos de clase I, 154 para los de clase II dr y 109 para los de clase II dq. Nuestro grupo de enfermos estuvo constituido por 72 pacientes, 60 mujeres y 12 varones, diagnosticados de artritis reumatoide según los criterios de la asociación americana de reumatismo (a.r.a., 1.988). En todos ellos se determino la presencia de factor reumatoide, así como la agresividad clínica de la enfermedad mediante la clasificación en estadios de steinbrocker (1.949). El estudio estadístico se ha realizado mediante el test exacto de Fisher. En los antígenos significativos en el presente estudio se ha calculado el riesgo relativo (woolf, 1.955) y el grado de asociación (bengtsson y thomson, 1.981). Hemos puesto de manifiesto en nuestros pacientes de artritis reumatoide un incremento significativo estadísticamente de los antígenos de clase II dr4, drw53 y dqw3. La susceptibilidad al padecimiento de la enfermedad se encontró mas firmemente unida en ellos a dqw3 que a dr4 y drw53. En nuestros pacientes de artritis reumatoide dqw3 se relaciono con los pacientes que tenían enfermedad más agresiva y limitante. Así mismo, dqw3 se asocio a la presencia de factor reumatoide, o sea, con los pacientes seropositivos. En los enfermos que presentaron manifestaciones tóxicas con la crisoterapia observamos un incremento valorable del antígeno de clase II dr3. También evidenciamos un aumento en ellos del antígeno de clase i b8, en desequilibrio de enlace con el anterior, mientras que dr7 parecía proteger frente a la toxicidad aurica. no hemos podido poner de manifiesto ningún antígeno dq que "predispusiera" o "protegiera" frente a la toxicidad de las sales de oroUniv. de Granada, Departamento de Medicina (Reumatología). Leída el 07-05-9

Molecular typing of canine parvovirus type 2 by VP2 gene sequencing and restriction fragment length polymorphism in affected dogs from Egypt

Introduction: Canine parvovirus-2 (CPV-2) is one of the most common infectious diseases in dogs characterized by severe gastroenteritis, vomiting, and bloody diarrhea. Little information is available about this topic in Egypt, particularly in the Delta region. This study reports the prevalence and molecular analysis of CPV-2 variants collected from El-Gharbia and Kafrelsheikh governorates in the Delta of Egypt. Methods: In this study, 320 rectal swabs were collected from infected domestic dogs from two districts in delta Egypt. The samples were investigated by rapid immunochromatographic test and polymerase chain reaction for detection the prevalence of CPV-2 variants. The genetic characterization was performed using restriction fragment length polymorphism (RFLP) analysis and partial VP2 gene sequence. Results and discussion: The viral antigen was detected in (264/320, 82.5%) of samples by IC test, while PCR was found more sensitive by detecting (272/320, 85%) positive samples. The RFLP technique using MboII restriction enzyme was successfully used for the differentiation of CPV-2c antigenic variants from CPV- 2a/2b strains. Interestingly, the molecular and phylogenetic analysis revealed that both CPV-2a and CPV-2c are circulating in the study area. Deduced amino acid sequence analysis showed changes at residue (N426E) and residue (T440A).: Our results indicated that CPV-2 is prevalent among dogs in Egypt, and therefore further molecular and epidemiological studies of CPV-2 are warranted.Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2023R23), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabi

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support.Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565EFPIA companiesJunta de Andalucia PI/0017/2016Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programmeEFPIAPostdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_2065