On an SE(Is)(Ih)AR epidemic model with combined vaccination and antiviral controls for COVID-19 pandemic.

In this paper, we study the nonnegativity and stability properties of the solutions of a newly proposed extended SEIR epidemic model, the so-called SE(Is)(Ih)AR epidemic model which might be of potential interest in the characterization and control of the COVID-19 pandemic evolution. The proposed model incorporates both asymptomatic infectious and hospitalized infectious subpopulations to the standard infectious subpopulation of the classical SEIR model. In parallel, it also incorporates feedback vaccination and antiviral treatment controls. The exposed subpopulation has three different transitions to the three kinds of infectious subpopulations under eventually different proportionality parameters. The existence of a unique disease-free equilibrium point and a unique endemic one is proved together with the calculation of their explicit components. Their local asymptotic stability properties and the attainability of the endemic equilibrium point are investigated based on the next generation matrix properties, the value of the basic reproduction number, and nonnegativity properties of the solution and its equilibrium states. The reproduction numbers in the presence of one or both controls is linked to the control-free reproduction number to emphasize that such a number decreases with the control gains. We also prove that, depending on the value of the basic reproduction number, only one of them is a global asymptotic attractor and that the solution has no limit cycles.

Estimation type results related to Fejér inequality with applications.

This paper deals with some new theorems and inequalities about a Fejér type integral inequality which estimate the difference between the right and middle part in Fejér inequality with new bounds. Also some applications to higher moments of random variables, an error estimate for trapezoidal formula, and some inequalities in connection with special means are given.

Some generalizations of Hermite-Hadamard type inequalities.

Some generalizations and refinements of Hermite-Hadamard type inequalities related to [Formula: see text]-convex functions are investigated. Also applications for trapezoid and mid-point type inequalities are given.

Single cell-derived clones from human adipose stem cells present different immunomodulatory properties.

Human adipose mesenchymal stem cells are a heterogeneous population, where cell cultures derived from single-cell-expanded clones present varying degrees of differential plasticity. This work focuses on the immunomodulatory/anti-inflammatory properties of these cells. To this end, five single-cell clones were isolated (generally called 1.X and 3.X) from two volunteers. Regarding the expression level of the lineage-characteristic surface antigens, clones 1·10 and 1·22 expressed the lowest amounts, while clones 3·10 and 3·5 expressed more CD105 than the rest and clone 1·7 expressed higher amounts of CD73 and CD44. Regarding cytokine secretion, all clones were capable of spontaneously releasing high levels of interleukin (IL)-6 and low to moderate levels of IL-8. These differences can be explained in part by the distinct methylation profile exhibited by the clones. Furthermore, and after lipopolysaccharide stimulation, clone 3.X produced the highest amounts of proinflammatory cytokines such as IL-1ß, while clones 1·10 and 1·22 highly expressed IL-4 and IL-5. In co-culture experiments, clones 1.X are, together, more potent inhibitors than clones 3.X for proliferation of total, CD3(+) T, CD4(+) T and CD8(+) T lymphocytes and natural killer (NK) cells. The results of this work indicate that the adipose stem cell population is heterogeneous in cytokine production profile, and that isolation, characterization and selection of the appropriate cell clone is a more exact method for the possible treatment of different patients or pathologies.

mTOR inhibitor monotherapy. A good treatment choice in renal transplantation?

Calcineurin inhibitors have reduced acute rejection rates and improved short-term graft survival, but without any improvement in long-term outcomes, since calcineurin inhibitors cause nephrotoxicity and death with a functioning graft. mTOR inhibitors have antiproliferative and anti-angiogenic effects with no nephrotoxicity. These properties could improve patient and graft long-term survival rates in select transplant recipients. In addition, monotherapy always diminishes the rate of non-compliance in chronic patients. We examined the evolution of 47 low immunological risk kidney transplant recipients with mTOR inhibitor monotherapy. The mean age was 45 ± 10 years (range: 18-69 years), with 25 males y 22 females. We performed an immunological evaluation before and at 3 and 12 months after starting monotherapy by detection of donor-specific antibodies by microsphere cytometry and the determination of lymphocyte activity with production of ATP by CD4+ T-lymphocytes activated by PHA mitogen. We considered patients to be of low immunological risk when the patient had an ATP production less than 520 ng/dl and no history of acute rejection episode or donor-specific antibodies. Initially, 5 patients received immunosuppression induction without calcineurin inhibitors (mycophenolate, prednisone, mTOR inhibitors and anti-CD25), and 42 were converted to mTOR inhibitors due to secondary effects of calcineurin inhibitors or malignancies. A total of 34 recipients had received sirolimus and 13 everolimus. Eighteen out 47 patients (38.2%) received prednisone and 29 (61.7%) mycophenolate with mTor before starting monotherapy. The mean follow-up period after starting monotherapy was 46.9 months (95% CI: 38.8-55.0 months). At the end of the follow-up, 7 out of 47 recipients (11.5%) had to change immunosuppression without losing their grafts after 1 year, due to heavy proteinuria in 2 cases, pulmonary infection in 1, acute rejection in 1, hepatotoxicity in 1, vasculitis in 1 and a temporary inclusion on dialysis after acute pyelonephritis in 1. Four out of 47 patients (8.5%) lost their grafts, as a result of chronic rejection in 3 cases, and as a result of death with a functioning graft in 1. The rate of acute rejection was 2.1%, one episode, which was solved with steroid pulses and switching from mTOR inhibitors to tacrolimus and mycophenolate. No patients developed donor-specific antibodies, and all of them maintained an ATP production less than 520 ng/dl. The rates of graft and recipient survival were both 100% at 1 year, and 88.7% and 95.7% at 5 years. The percentages of patients on monotherapy were 97.9% and 70.5 % at 1 and 5 years, respectively. At the end of the follow-up, 36 out of 47 recipients remained on mTOR inhibitor monotherapy. Serum creatinine and glomerular filtration rates improved significantly, from 2.16 ± 1.05 mg/dl to 1.49 ± 0.56 mg/dl (P=.001) and from 39.23 ± 25.23 ml/min to 52.23 ± 23.20 ml/min (P=.001), respectively. Proteinuria increased but not significantly, from 306.6 ± 400 mg/24h to 418.1 ± 514.1mg/24h (P=.17). The patients treated with mTOR inhibitors received significantly more erythropoietin and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers than before starting mTOR, but there was no change in the treatment with statins or hypotensive agents. Body weight and the percentage of diabetic recipients were similar during the study. No cases of non-compliance were observed during the follow-up. The present study supports the safety and efficacy of monotherapy with mTOR inhibitors in select kidney transplant recipients.

A stable multimodel scheme control for the regulation of the transient behavior of a tunnel-diode trigger circuit.

A multimodel scheme is designed for a triggering tunnel-diode circuit. The scheme improves the transient behavior during the transition time period after switching from a stable system equilibrium point to another one which is known as a triggering process. Each model is obtained by a linearization of the circuit near an equilibrium point. Moreover, each of these models can be described as a combination of two other transfer functions describing the linearized plant behavior near two different equilibrium points. The scheme chooses online the model with the best tracking performance in order to generate the control law. Different reference transfer functions are proposed with the aim of generating the desired transient in the triggering process. Some simulations show the usefulness of this scheme.

[Pulmonary valvular agenesis treated with cryopreserved pulmonary homograft]. / Agenesia valvular pulmonar tratada con homoinjerto pulmonar crioconservado.

We report successful treatment of pulmonary valve agenesia with pulmonary stenosis and ventricular septal defect by infundibular resection, patch-closure of the VSD and implantation of a cryopreserved pulmonary homograft. Cases with mild to moderate hypoplasia of the pulmonary annulus are particularly well suited for direct pulmonary homograft implantation, while cases with severe hypoplasia and high right ventricular pressure after correction may be better treated with aortic homografts. Some technical aspects of homograft implantation (doing first the proximal suture, preserving the normal configuration of the valvular sinuses and using the subvalvular homograft tissue to enlarge the right ventricular outflow tract) may prevent significant valvular incompetence.

[A genetic and hormonal study of 5 patients with the nonclassical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency]. / Estudio genético y hormonal de 5 pacientes afectados de la forma no clásica de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa.

BACKGROUND: To study the association between the 21-hydroxylase deficiency with the HLA histocompatibility complex in a mediterranean ethnic group. METHODS: 5 patients with late-onset 21-hydroxylase deficiency, diagnosed on the basis of a high plasma level of 17-hydroxyprogesterone, along with 23 family members were typed. 17-hydroxyprogesterone response to iv ACTH stimulus was measured too in the family members. RESULTS: We found a genetic linkage disequilibrium between the late-onset 21-hydroxylase deficiency and the HLA antigen B51. Moreover, similar biologic profiles were observed in the patients and those of their siblings who were HLA identical. The heterozygous carriers showed a intermediate 17-hydroxyprogesterone response to ACTH between propositus and homozygotes and their family members who had no HLA haplotype identical to those of the propositus. CONCLUSIONS: These observations tend to confirm that a close linkage exits between the gene (or genes) for 21-hydroxylase deficiency in late-onset adrenal hyperplasia and the HLA genes. This association may change in the different ethnic groups.

Human in vivo-induced spontaneous IgG-secreting cells from tonsil, blood and bone marrow exhibit different phenotype and functional level of maturation.

The subset of human spontaneous IgG-secretion cells consists of mature B lymphocytes which are capable of active and high rate IgG production in vitro without the need for additional stimuli. Therefore, such a cell subset provides a useful model for studying the terminal stages of B-cell maturation. The present work analyses the phenotypic and functional characteristics of spontaneous IgG secreting cells obtained from tonsil, blood and bone marrow. The tonsilar cell subset was CD9+ CD20+ CD19+ CD38+/-, the blood cell subset CD9- CD20- CD19+ CD38+/- and bone marrow cells were CD9- CD20- CD19+/- CD38+. The three cell subsets required de novo RNA and protein synthesis for IgG secretion to occur. Tonsilar and blood, but not bone marrow, subsets also required DNA synthesis to undergo IgG secretion. Kinetics studies revealed that IgG production by tonsil and blood cells reached a plateau after 3 days of culture. In contrast, the bone marrow cell subset secreted IgG in a linear fashion for 2 weeks. These results indicate that spontaneous IgG-secreting cells from different organs exhibit functional and phenotypic heterogeneity.

Differential effect of anti-HLA class I monoclonal antibodies on resting and in vivo-induced B lymphocytes.

The role of HLA class I antigens in B cell triggering was investigated by analyzing the effect of monoclonal antibodies (MAbs) directed to such molecules on the in vitro function of resting and in vivo-induced lymphoblastoid (LB) B cells. Staphylococcus aureus Cowan I (SAC)-induced proliferation of high-density B lymphocytes was markedly inhibited by W6/32 MAb (reactive with a monomorphic determinant contributed by an alpha-chain and beta 2-microglobulin) but not by FG2/2 MAb (reactive with beta 2-microglobulin). The inhibition was not due to either a toxic effect or a change in the response kinetics. In contrast, LB B cells' spontaneous DNA synthesis and IgG production was not altered by such MAb, although these cells possessed surface HLA class I antigens. These findings suggest that HLA class I molecules are involved in the activation process of resting but not mature B lymphocytes.

Human B lymphocytes capable of spontaneous Ig production in short-term cultures. II. Relationship with the spontaneous DNA-synthesizing B cells.

It has been previously demonstrated that normal nonimmunized individuals possess circulating and tissular B cells, which are capable of spontaneous immunoglobulin (Ig) production in short-term (3 days) cultures. We have also observed the occurrence of low levels of [3H]thymidine uptake early in such cultures. This work analyzes the relationship between both spontaneous B-cell functions in vitro: Kinetics studies revealed that both activities were temporarily related, as spontaneous DNA synthesis was maximal from 8 to 12 hr, and declined thereafter, when spontaneous Ig secretion was first detected in the culture supernatant: The abrogation of DNA synthesis at the culture initiation or during the period of early proliferation, but not after 24 hr, inhibited subsequent IgG secretion. The B cells responsible for spontaneous DNA synthesis and IgG secretion exhibited similar low densities, since both were recovered in the 42.5-45% Percoll fractions, and identical large size as determined by 1g sedimentation procedure, and in tonsil, were equally reactive with the BA-2 mouse monoclonal antibody. Finally, limiting dilution analysis showed that the precursor frequencies of both cells under study were similar. These results suggest that spontaneous DNA synthesis and IgG production are carried out by the same subset of in vivo-preactivated lymphoblastoid B cells.

Abnormal B cell function in haemophiliacs and their relationship with factor concentrates administration.

The present study was performed to evaluate B cell function in haemophiliacs. Spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin (Ig) production was determined by ELISA in the supernatants of cultured peripheral blood lymphocytes (PBL) from 14 haemophiliacs and 17 normal donors. Spontaneous IgM, IgA and IgG production was three times higher in patients than normal controls, while PWM-induced IgM, IgA and IgG production was markedly reduced in patients compared to normal donors (P less than 0.025). Allogeneic co-cultures of haemophiliacs and normal B plus T cell fractions revealed that these results are due to a defect of the patients' T cell depleted fraction. These abnormalities were not found in three patients who had received no clotting factor concentrates for at least 1 year prior to the study. Additionally, the annual amount of clotting factor concentrates received by treated patients correlates well with the enhancement of spontaneous Ig production (r = +0.688, P less than 0.02), the decrease of PWM-induced Ig secretion (r = -0.655, P less than 0.02), and the elevation of serum IgG levels (r = +0.610, P less than 0.05). These findings suggest that the administration of clotting factor concentrates play an important role in the altered B cell function in haemophiliacs.