MIF is a common genetic determinant of COVID-19 symptomatic infection and severity.

BACKGROUND: Genetic predisposition to coronavirus disease 2019 (COVID-19) may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity. AIM: To determine associations of common functional polymorphisms in MIF with symptomatic COVID-19 or its severity. METHODS: This retrospective case-control study utilized 1171 patients with COVID-19 from three tertiary medical centers in the USA, Hungary and Spain, together with a group of 637 pre-pandemic, healthy control subjects. Functional MIF promoter alleles (-794 CATT5-8,rs5844572), serum MIF and soluble MIF receptor levels, and available clinical characteristics were measured and correlated with COVID-19 diagnosis and hospitalization. Experimental mice genetically engineered to express human high- or low-expression MIF alleles were studied for response to coronavirus infection. RESULTS: In patients with COVID-19, there was a lower frequency of the high-expression MIF CATT7 allele when compared to healthy controls [11% vs. 19%, odds ratio (OR) 0.54 [0.41-0.72], P < 0.0001]. Among inpatients with COVID-19 (n = 805), there was a higher frequency of the MIF CATT7 allele compared to outpatients (n = 187) (12% vs. 5%, OR 2.87 [1.42-5.78], P = 0.002). Inpatients presented with higher serum MIF levels when compared to outpatients or uninfected healthy controls (87 ng/ml vs. 35 ng/ml vs. 29 ng/ml, P < 0.001, respectively). Among inpatients, circulating MIF concentrations correlated with admission ferritin (r = 0.19, P = 0.01) and maximum CRP (r = 0.16, P = 0.03) levels. Mice with a human high-expression MIF allele showed more severe disease than those with a low-expression MIF allele. CONCLUSIONS: In this multinational retrospective study of 1171 subjects with COVID-19, the commonly occurring -794 CATT7MIF allele is associated with reduced susceptibility to symptomatic SARS-CoV-2 infection but increased disease progression as assessed by hospitalization. These findings affirm the importance of the high-expression CATT7MIF allele, which occurs in 19% of the population, in different stages of COVID-19 infection.

[Genotypes of hepatitis C virus: their relationship with risk factors, the severity of liver disease, and the serologic response]. / Genotipos del virus de la hepatitis C: relación con los factores de riesgo, con la gravedad de la enfermedad hepática y con la respuesta serológica.

BACKGROUND: The objective of our study was to ascertain the prevalence of different HCV genotypes between the hepatitis C patients in the health area of Monforte de Lemos, Spain, as well as the possible influence of risk factors on their distribution and their relation with hepatic disease and with the serologic response. PATIENTS AND METHODS: We have studied 128 patients with hepatitis C. Of these, 41 were intravenous drug users (IVDU), 19 had received transfusions, 7 were hemodialyzed and in 61 the risk factors were unknown. Antibodies against HCV were detected by second-generation enzyme immunoassay (EIA) and confirmed by immunoblot. RNA-HCV presence was studied by reverse transcription-PCR (RT-PCR), and a reverse hybridization test of the amplifications was used for the genotyping. RESULTS: Hepatitis C genotypes 1b (46.1 [8.6%]), 1a (23.4 [7.3%]) and 3a (13.3 [5.9%]) were the most frequently encountered genotype. Genotype 1a (48.8 [15.3%]) was the most prevalent genotypes in IVDU patients, while 1b was the most frequent in patients of unknown risk factors (62.3 [12.1%]). Alanine-aminotransferase (ALT) was elevated in 66.6 (17.7%) of patients with genotype 1a, in 87.5 (8.6%) of patients with genotype 1b (p = 0.0367) and in 94.1 (11.2%) of patients with genotype 3a (p = 0.0347). Subtype 1b was present in 6 of 7 cases of cirrhosis (85.7%) and in 7 of 12 cases of active chronic hepatitis (58.3%). No significant statistical differences were observed between the genotypes and the specific IgM response against core antigen of HCV, neither we observed differences in the serologic response against C1, C2, NS3 and NS4 peptides. CONCLUSIONS: Hepatitis C genotypes 1a and 3a were the most prevalent genotypes between IVDU patients while genotype 1b was the most frequent between non-IVDU patients. Genotype 1b was associated to severe liver disease. Percentage of positivity or the reactivity against HCV peptides was independent of the genotype encountered in the patient.

[Laboratory diagnosis and serologic course in patients with tularemia]. / Diagnóstico de laboratorio y evolución serológica de pacientes con tularemia.

BACKGROUND: Tularemia was practically unknown in Spain until the end of 1997, when an epidemic outbreak was declared. This paper presents the data on microbiological diagnosis of 55 patients who suffered from tularemia. PATIENTS AND METHODS: Thirty-two samples from 19 patients and 151 serum samples from 55 patients were obtained for culture. Serologic diagnosis was performed by tube sero-agglutination and microagglutination. Three types of tests were performed on all sera: Wright sero-agglutination (WSA), Coombs test against Brucella spp. and sero-agglutination against Yersinia enterocolitica O:3, Yersinia enterocolitica O:3, and Proteus OX 19. RESULTS: F. tularensis was found in two samples (6.25%) of the 32 received. Titers > or = 1/160 were obtained in 78.2% and 74.5% of the initial sera by tube sero-agglutination and microagglutination, respectively. Correlation between the two tests was 0.80 (p < 0.001). Prozone phenomenon was observed in 59.9% of the sera, while crossed reactivity to Brucella spp. and Proteus spp. was found in 9.3% and 22.8%, respectively. No crossed reactivity was observed with Yersinia spp. CONCLUSIONS: Culture of F. tularensis has low sensitivity. The correlation obtained between tube sero-agglutination and microagglutination is good. Both techniques are useful in routine diagnosis of tularemia, although microagglutination has some advantages over tube agglutination.

Understanding staff nurse responses to change: utilization of a grief-change framework to facilitate innovation.

This paper reviews the literature on the psychological effects of change and discusses the impact of an overarching organizational change on the staff nurses of a large oncology unit in the Midwest. Their reactions are compared with a grief-change framework synthesized from the literature. This framework was useful in explaining staff nurse behaviors and attitudes, and offered interventions specific to each stage of the change process useful to the CNS. Dissemination of this information is discussed, as well as implications for advanced nursing practice.

Autoimmune progesterone dermatitis: a complex case

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[Surgical management of Pott's paraplegia]. / Manejo quirúrgico de la paraplejía póttica.

A series of 19 patients suffering Pott's paraplegia was reviewed in a ten-year period. Ever since their admission they were submitted to an antiphthisic and orthopedic medical treatment for 3 to four weeks. A medullar decompression by reaching the focus through different surgical technics was performed on 16 of them. 3 did not require such procedure; 14 recovered completely; 2 partial recovery and 3 did not recover at all. The degree of kyphosis together with affected vertebrae and area, plus ossifluent abscess, the lack of sphincter control and pre-treatment evolution were correlated with recovery from paraplegia.

Hydatid cyst of the lung: diagnosis and treatment.

Hydatid infestation of the lung can be primary or secondary. In three of four cases the cyst is a single one. Hydatidosis of a different location, particularly the liver, may be associated. The period of initial growth of primary hydatidosis is frequently asymptomatic. Bronchial fistulization is an important event in the evolution of the cyst. Intrapleural rupture constitutes a rare eventuality, but it is often as characteristic as it is severe. Secondary, metastatic hydatidosis, due to breaking of a primary visceral cyst in a vein or heart, is rare. A special form is so-called multiple malignant pulmonary hydatidosis, which causes progressive respiratory deficiency and right ventricular failure. There are a variety of radiographic images. Ultrasonography, computed tomography, and magnetic resonance imaging can recognize certain details of the lesions and discover others that are not visible by conventional radiography. For a specific serologic diagnosis, our experience favors the immunoglobulin G enzyme-linked immunosorbent assay and immunoelectrophoresis. Treatment is essentially surgical. In general, chemotherapy is used as a complement to operative treatment to avoid recurrence. Surgery has two objectives: to remove the parasite and to treat the bronchipericyst pathology and other associated lesions. The prognosis has changed during the last few years, and results are now commonly satisfactory. The most frequent complications are pleural infection and prolonged air leakage. Operative mortality does not exceed 1% to 2%. Despite the low mortality and the limited recurrence rate, it is necessary to remember the invading character of pulmonary hydatid disease, which sometimes makes therapy difficult and questionable. Prophylaxis is essential to eradicate the disease completely.

Clinical evaluation of a commercial ligase-based gene amplification method for detection of Mycobacterium tuberculosis.

The purpose of this study was to evaluate the clinical usefulness of a commercial ligase-based gene amplification method (LCx Mycobacterium tuberculosis test; Abbott Laboratories, USA) for detection of Mycobacterium tuberculosis. The tuberculosis infection rate among clinical samples was 10.6%. The sensitivity, specificity, and positive and negative predictive values were 23.5%, 100%, 100%, and 91.7%, respectively, with the fluorochrome auramine stain; 32.4%, 100%, 100%, and 92.6%, respectively, with culture; and 76.5%, 95.8%, 68.4% and 97.2%, respectively, with the gene amplification method. When only samples from patients without current or previous treatment were studied, the sensitivity was 36.4% with the auramine stain, 63.6% with culture, and 100% with the gene amplification assay. The mean treatment time for culture-negative and assay-negative samples was greater than that of culture-negative and assay-positive samples. The LCx Mycobacterium tuberculosis test is a sensitive method for detection and identification of Mycobacterium tuberculosis. It produces few false-positive results. However, as it can remain positive after the culture becomes negative, it is not recommended for evaluation of treatment efficiency.

Inhibition of the degranulation and myeloperoxidase activity of human polymorphonuclear neutrophils by Brucella melitensis.

The degranulation and myeloperoxidase-H2O2-halide activities of human polymorphonuclear leukocytes from healthy donors were tested after co-incubation with either Brucella melitensis 16M, Staphylococcus aureus or Staphylococcus aureus in presence of lipopolysaccharide, protein fraction, native hapten and soluble fractions released at 65 degrees C from smooth strain of Brucella melitensis 16M. The degranulation and myeloperoxidase activities of polymorphonuclear leukocytes were significantly higher when co-incubated with Staphylococcus aureus than with Brucella melitensis. The presence of lipopolysaccharide, protein fraction, and native hapten did not cause significant modification of either degranulation or myeloperoxidase activities of polymorphonuclear leukocytes against Staphylococcus aureus. Soluble fraction released at 65 degrees C produced a significant reduction in the myeloperoxidase activity but did not alter the degranulation of polymorphonuclear leukocytes triggered by Staphylococcus aureus.

Comparative sensitivity of six serological tests and diagnostic value of ELISA using purified antigen in hydatidosis.

Most serodiagnostic techniques have been evaluated for diagnosis of cystic hydatid disease caused by Echinococcus granulosus. Each, to varying degrees, has been shown to give false results, with considerable variation between laboratories. The comparative study was made concerning the sensitivity of the immunodiagnostic methods based on 58 sera from hydatid disease with different cyst locations. Latex agglutination, immunoelectrophoresis (IEP), and specific IgE, IgG enzyme-linked immunosorbent assay (ELISA) tests were studied. Specific IgG ELISA AgB (antigen B-rich fraction) was the most sensitive test (96.5%) and the least sensitive tests were specific IgE ELISA (24.1%) and IEP (25.8%). The low sensitivity of these two tests was due partly to the low reactivity detected in the sera of patients with lung hydatidosis. Initial laboratory studies showed purified antigens to be preferable to crude cyst fluid, regardless of the type of test used. For this reason, we evaluated the sensitivity and specificity of ELISA by using the purified antigen-B-rich fraction. In all, 117 sera were examined: 78 sera from patients with hydatidosis surgically confirmed, 15 sera from healthy control subjects, and 24 sera from patients with diseases other than hydatidosis. The method gave good results: 93.5% sensitivity, 89.7% specificity, and 92.3% diagnostic efficacy.

Specificity of a polymerase chain reaction assay of a target sequence on the 31-kilodalton Brucella antigen DNA used to diagnose human brucellosis.

The aim of this study was to evaluate the specificity of a polymerase chain reaction assay for detecting Brucella DNA using primers specific for the amplification of a 223 bp region of the sequence encoding a 31 kDa immunogenic Brucella abortus protein (BCSP31). DNA from all Brucella strains, including type, reference, vaccine and field strains, were correctly amplified. With the exception of Ochrobactrum spp., no other amplification was detected with a broad panel of microorganisms serologically or phylogenetically related to Brucella spp. This very good degree of specificity, together with its high yield demonstrated in previous clinical studies, confirms that this polymerase chain reaction assay could be a useful tool for the diagnosis of human brucellosis.

Brucella lipopolysaccharides induce cyclooxygenase-2 expression in monocytic cells.

Human brucellosis is characterized by the presence of both acute inflammatory episodes and chronic inflammation with granuloma formation. On this basis, the proinflammatory effects of smooth lipopolysaccharide of Brucella (S-LPS) were addressed and compared to those of LPS from Escherichia coli. For this purpose, the induction of cyclooxygenase-2 (COX-2), the production of the chemokine monocyte chemoattractant protein-1 (MCP-1), and the activation of the nuclear factor kappa B (NF-kappa B) were studied. S-LPS was found to induce both COX-2 expression and MCP-1 production; however, the potency of E. coli LPS exceeded that of Brucella S-LPS by some orders of magnitude. However, at concentrations above 1 microg/ml, all of the LPS produced comparable effects, including their ability to activate the NF-kappa B system. These observations help explain the inflammatory events associated with Brucella infection and the ability of Brucella to produce monocyte recruitment and granuloma formation.

Lipopolysaccharides of Brucella abortus and Brucella melitensis induce nitric oxide synthesis in rat peritoneal macrophages.

Smooth lipopolysaccharide (S-LPS) and lipid A of Brucella abortus and Brucella melitensis induced the production of nitric oxide (NO) by rat adherent peritoneal cells, but they induced lower levels of production of NO than Escherichia coli LPS. The participation of the inducible isoform of NO synthase (iNOS) was confirmed by the finding of an increased expression of both iNOS mRNA and iNOS protein. These observations might help to explain (i) the acute outcome of Brucella infection in rodents, (ii) the low frequency of septic shock in human brucellosis, and (iii) the prolonged intracellular survival of Brucella in humans.

Infection by hepatitis B and C virus in non-intravenous drug using female prostitutes in Spain.

We have studied the prevalence of hepatitis B (HBV) and hepatitis C virus (HCV) serologic markers in female blood donors and in female prostitutes and the relationship of antibodies to hepatitis B core antigen (anti-HBc) and of antibodies to HCV (anti-HCV) with the presence of treponemal antibodies (FTA-ABS) in non-intravenous drug using female prostitutes. Hepatitis B surface antigen (HBsAg) was found in 1.0% of the female blood donors, anti-HBc in 15.6% and anti-HCV in 0.7%. In the prostitutes, the prevalence of HBsAg was 6.1%, anti-HBc was positive in 29.0% and anti-HCV in 8.8%. No significant statistical association between the prevalence of anti-HBc or anti-HCV and the age of prostitutes (p = 0.9111 and p = 0.8254 respectively) or the length of time as prostitutes (p = 0.3583 and p = 0.5770) was found. FTA-ABS positive prostitutes had a significantly higher prevalence of anti-HCV than FTA-ABS negative prostitutes (p < 0.001). No statistical association was found between anti-HBc antibodies and positive FTA-ABS prostitutes (p = 0.336).

Prevalence of anti-hepatitis C virus antibodies in positive FTA-ABS non-drug abusing female prostitutes in Spain.

The prevalence of antibodies against Hepatitis C Virus (anti-HCV antibodies) and its association with the presence of treponemal antibodies (FTA-ABS) was studied in 227 non-drug abusing female prostitutes. The overall anti-HCV antibody prevalence was 8.8%, and a significantly higher prevalence of anti-HCV antibodies was found in prostitutes testing positive for FTA-ABS (19.4%) than in prostitutes testing negative for FTA-ABS (3.9%) (PR = 5.023, P less than 0.001). No statistical association was found between patient age or the duration of prostitution and the presence of anti-HCV antibodies.