Simulating the impact of non-pharmaceutical interventions limiting transmission in COVID-19 epidemics using a membrane computing model.

Epidemics caused by microbial organisms are part of the natural phenomena of increasing biological complexity. The heterogeneity and constant variability of hosts, in terms of age, immunological status, family structure, lifestyle, work activities, social and leisure habits, daily division of time and other demographic characteristics make it extremely difficult to predict the evolution of epidemics. Such prediction is, however, critical for implementing intervention measures in due time and with appropriate intensity. General conclusions should be precluded, given that local parameters dominate the flow of local epidemics. Membrane computing models allows us to reproduce the objects (viruses and hosts) and their interactions (stochastic but also with defined probabilities) with an unprecedented level of detail. Our LOIMOS model helps reproduce the demographics and social aspects of a hypothetical town of 10 320 inhabitants in an average European country where COVID-19 is imported from the outside. The above-mentioned characteristics of hosts and their lifestyle are minutely considered. For the data in the Hospital and the ICU we took advantage of the observations at the Nursery Intensive Care Unit of the Consortium University General Hospital, Valencia, Spain (included as author). The dynamics of the epidemics are reproduced and include the effects on viral transmission of innate and acquired immunity at various ages. The model predicts the consequences of delaying the adoption of non-pharmaceutical interventions (between 15 and 45 days after the first reported cases) and the effect of those interventions on infection and mortality rates (reducing transmission by 20, 50 and 80%) in immunological response groups. The lockdown for the elderly population as a single intervention appears to be effective. This modeling exercise exemplifies the application of membrane computing for designing appropriate multilateral interventions in epidemic situations.

Effects of pomegranate juice in circulating parameters, cytokines, and oxidative stress markers in endurance-based athletes: A randomized controlled trial.

OBJECTIVE: The aim of the present study was to assess the effects of pomegranate juice on the level of oxidative stress in the blood of endurance-based athletes. Pomegranate juice is rich in polyphenols, conferring it a higher antioxidant capacity than other beverages with polyphenolic antioxidants. METHODS: A randomized double-blind, multicenter trial was performed in athletes from three different sport clubs located in southeastern of Spain. Plasma oxidative stress markers (protein carbonyls and malondialdehyde [MDA]) as well as C-reactive protein and sE-selectin were measured. Thirty-one athletes participated in the study. Participants were divided into three groups. The first group was supplemented with 200 mL/d pomegranate juice (PJ; n = 10) over a 21-d period, the second with 200 mL/d pomegranate juice diluted 1:1 with water (PJD; n = 11), and a control group that did not consume pomegranate juice (C; n = 10). Nine athletes were excluded due to protocol violations (n = 4 in the PJ group and n = 5 in the PJD group) because they did not observe the 24 h of rest before the last blood test. RESULTS: The control group increased levels of carbonyls (+0.7 ± 0.3 nmols/mg protein) and MDA (+3.2 ± 1.0 nmols/g protein), whereas the PJ and PJD groups maintained or decreased their levels, respectively. On the other hand, lactate levels increased in the PJ group (from 10.3 at day 0 to 21.2 mg/dL at day 22). A nonsignificant decrease was detected in sE-selectin and C-reactive protein in the groups consuming pomegranate juice. CONCLUSION: Consumption of pomegranate juice over a 21-d period improved MDA levels and carbonyls, and thus decreased the oxidative damage caused by exercise.

Importance of exercise in the control of metabolic and inflammatory parameters at the moment of onset in type 1 diabetic subjects.

The onset of type 1 diabetes coincides with the final phase of ß-cell destruction. In some cases, this period is characterized by the presence of a functional reserve of ß-cells, favouring an adequate metabolic control (honeymoon phase). Therefore, the extension of this situation could have evident benefits in subsequent diabetes management. We aimed to study the influence of regular physical activity before and after the onset of the disease. We did an observational study of 2 groups of type 1 diabetic patients from onset to a 2-year period. One group (n = 8) exercised regularly (5 or more hours/week) before onset and continued doing so with the same regularity. The second group (n = 11) either did not perform physical activity or did so sporadically. Circulating glycated haemoglobin (HbA1c), C-peptide, protein carbonyls and basal cytokine levels were determined at the beginning and at the end of the 1(st) and 2(nd) year. The more active group debuted with and maintained significantly lower HbA(1c) levels and insulin requirements compared to the more sedentary group. C-peptide levels were only significantly higher in the active group at the moment of onset compared to the sedentary group. In addition, determination of basal circulating cytokines revealed a large variability between individuals but no significant differences when comparing the groups. Altogether, the obtained results seem to indicate that physical activity allows a better control at the moment of onset regarding glycaemic control, residual endocrine pancreatic mass and subsequent insulin requirements.

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.

Discriminating farmed gilthead sea bream Sparus aurata and European sea bass Dicentrarchus labrax from wild stocks through scales and otoliths.

The study of mass and standard length (L(S) ) relationships showed that farmed individuals had higher values than wild fishes for both gilthead sea bream Sparus aurata and European sea bass Dicentrarchus labrax. Such differences were more pronounced in larger individuals than smaller ones and were more noticeable in S. aurata than in D. labrax. Additionally, differences in external characteristics of scales were detected between origins. A high proportion of farmed S. aurata had a regenerated nucleus (98%) and scale malformations (73%), and there were no annual rings in the farmed D. labrax (100%). Variation in otolith morphology was examined through shape descriptors such as area, perimeter, circularity, roundness, mass, height and length relationship and elliptic Fourier descriptors (EFDs). Important differences were found within geographical origins according to each shape descriptor separately, but no clear patterns distinguished wild and farmed fish. Discriminant analysis with either all shape descriptors together or EFDs was able to classify with high accuracy both S. aurata (89·5-95·7%) and D. labrax (93·2-95·2%) according to their origin. Hence, this study suggests the use of scale characteristics as the easiest and quickest way to distinguish farmed or escaped fishes, and secondly, the usefulness of EFDs or shape descriptors to improve such separation.

Emulsion polymerization of vinyl acetate: safe optimization of a hazardous complex process.

Fast and exothermic discontinuous emulsion polymerization processes are particularly difficult to optimize from both safety and productivity point of view because of the occurrence of side undesired reactions (e.g. chain transfer to monomer, backbiting, propagation of tertiary radicals, termination by disproportion, etc.) and the hazards of boiling phenomena and stable foam formation under atmospheric pressure. Moreover, the relevant number of loading, heating and cooling steps, required before starting the monomer addition (that is, the desired reaction), makes a strict product quality reproducibility very difficult to obtain. Under these operating conditions, it is necessary to employ a suitable combined theoretical and experimental procedure able to detect the optimum process dosing time at both the laboratory and the industrial scale. In this work, it is shown how to use the topological criterion theory together with proper adiabatic calorimeter and RC1 experimental data to safely optimize the synthesis of polyvinyl acetate through the radical emulsion polymerization of vinyl acetate by the means of an indirectly cooled isoperibolic semibatch reactor.

Radiographic morphometric study of 37 periapical lesions in 30 patients: validation of success criteria.

PURPOSE: The purpose of this study was to establish the midterm prognosis of periapical surgery by use of the ultrasound technique, comparing a scale obtained by image analysis with the success rates according to other prognostic scales. MATERIALS AND METHODS: A clinical follow-up study was performed between September 2004 and September 2005. Thirty-six patients with chronic periapical lesions were treated with periapical surgery via the ultrasound technique and root-end filling with silver amalgam. Evolution was analyzed by use of the different currently accepted assessment scales at 6 and 12 months after intervention with a scale obtained by radiographic image analysis. RESULTS: Thirty patients with a mean age of 40.5 years were studied. The mean follow-up period was 14.2 months. Thirty-seven lesions were analyzed. A positive correlation at 6 months was observed between the radiographic scale proposed in this study and the scales of Rud and Andreasen and von Arx et al. At 12 months, the proposed radiographic scale only correlated with the functional tooth concept established by Friedman. CONCLUSIONS: There was no statistically significant relation between the radiographic scale from the image analyzer and the criteria of Rud and Andreasen and von Arx et al.

[Familial exudative vitreoretinopathy: our experience]. / Vitreorretinopatía exudativa familiar: nuestra experiencia.

PURPOSE: To describe our experience in the diagnosis of Familial Exudative Vitreoretinopathy (FEVR) at its different clinical stages. We also report our outcomes in early treatment of this inherited disorder. METHODS: Retrospective interventional and descriptive case series of 11 patients (17 eyes) affected by FEVR evaluated and treated in our hospital. RESULTS: In our series, 33.3% of patients were classified as stage I, while 16.7% and 50% were classified as stage II and III, respectively. Visual acuity (VA) remained stable after treatment in stages I and II (mean VA was 0.8 and 0.4, respectively) but decreased in stage III. CONCLUSIONS: Early treatment of FERV may improve the visual prognosis and avoid complications such as subfoveal chronic exudation and vitreoretinal peripheral interphase contraction and fibrosis.

Changes in amphipod (Crustacea) assemblages associated with shallow-water algal habitats invaded by Caulerpa racemosa var. cylindracea in the western Mediterranean Sea.

The effects of the invasive species Caulerpa racemosa var. cylindracea (hereafter C. racemosa) on amphipod assemblages associated with shallow-water rocky habitats were studied. Two habitats located along the SE Iberian Peninsula were compared; invaded and non-invaded. The results showed that growth of C. racemosa affects habitat structure, influencing the species composition and biomass of macroalgae, and detritus accumulation. In turn, such changes in habitat features affected the associated amphipod assemblages with different ecological requirements. However, the species richness of amphipods was relatively high in both habitats, while the species composition of amphipods changed completely. For example, some species such as Ampithoe ramondi and Hyale schmidti did not colonize invaded habitats, while others such as Apocorophium acutum were favoured by the spread of C. racemosa. Habitat invasion by C. racemosa can have an important influence on biotic assemblages, modifying both habitat structure and the associated fauna, with unknown effects on the overall ecosystem.

[Complications of endoscopic retrograde cholangiopancreatography in patients aged more than 90 years old]. / Complicaciones de la colangiopancreatografía retrógrada endoscópica en pacientes mayores de 90 años.

INTRODUCTION: To evaluate the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and the complication rates of this procedure in patients aged 90 years and older. PATIENTS AND METHOD: A descriptive, prospective study including 42 endoscopic procedures performed from first January 2001 until first June 2004 in 36 patients (7 males and 29 females) was performed. The mean age was 91 years (range 90-96 years). All patients underwent the following: a) clinical evaluation before and after endoscopic exploration; b) evaluation of the success or failure of the endoscopic procedure and c) assessment of complications (perforation, hemorrhage, pancreatitis and infection). Concurrent associated illnesses, as well as the existence of anatomical alterations in Vaters papilla (duodenal diverticula), were also evaluated. RESULTS: ERCP was successful in 85.7% of all explorations performed. Twenty-three patients (63.8%) had one or more major associated diseases. In 15 patients (33.3%) Vaters papilla was associated with duodenal diverticula. The complication rates were as follows: 1) acute pancreatitis in 2 explorations (4.7%), one mild (2.35%) and the other moderate (2.35%); 2) hemorrhage after endoscopic sphincterotomy in 2.8% of patients (1/35); 3) bacteriemia in one patient (2.3%) and cholangitis in one patient (2.3%), with no cases of secondary cholecystitis; 4) hypoxemia in one patient. There were no perforations or deaths related to the procedure. CONCLUSION: ERCP is a safe and effective technique with a low complication rate in patients aged 90 years or older.

Plasma cell granuloma of the thyroid and Hashimoto thyroiditis.

Plasma cell granuloma of the thyroid is a rare tumor-like lesion formed by a localized proliferation of inflammatory cells, supported by a stroma of fibrous tissue. Few cases have been previously reported in the medical literature. We report a new case of a 41-year-old man presenting a goiter with primary hypothyroidism (thyroid-stimulating hormone, 70 mIU/L; free thyroxine, < 0.01 pmol/L; triiodothyronine, 0.66 nmol/L) and elevation of thyroid antibodies. Several fine-needle aspiration biopsies of the thyroid were fruitless and total thyroidectomy was performed. Histologic and immunohistochemical study demonstrated the polyclonal nature of the cells and yielded a diagnosis of plasma cell granuloma. Histologic findings of Hashimoto thyroiditis were present too.

Acute phase response in patients undergoing lumbar spinal surgery: modulation by perioperative treatment with naproxen and famotidine.

In orthopaedic surgery, perioperative administration of non-steroidal anti-inflammatory drugs has been shown to reduce postoperative pain and analgesic consumption. In addition, preoperative administration of ibuprofen has proved to reduce interleukin-6 (IL-6) release, while that of ranitidine reduced postoperative IL-6-induced C-reactive protein synthesis in patients undergoing abdominal surgery. However, it has not been established whether the preoperative administration of both types of drugs may reduced the postoperative inflammatory reaction after instrumented spinal surgery. Accordingly, our objective was to investigate the effects of preoperative treatment with naproxen plus famotidine on the postoperative systemic inflammatory reaction in patients undergoing instrumented lumbar spinal surgery. Forty consecutive patients scheduled for elective instrumented spinal fusion were alternately assigned to receive either naproxen (500 mg/day, p.o.) plus famotidine (40 mg/day, p.o.) for 7 days before operation, or no adjuvant treatment. Haematological parameters, acute phase proteins, complement fractions, immunoglobulins and cytokines were determined 7 days and immediately before surgery, and on days 0, 1, 2 and 7 after surgery. Haematological parameters, clinical data, duration of surgery, blood loss, perioperative blood transfusion and postoperative complications were similar in the two groups, although pretreated patients showed lower increases in body temperature and required less analgesic medication. Compared with preoperative levels, IL-6 levels were significantly increased postoperatively in all patients with no differences between groups. C-reactive protein, alpha(1)-acid-glycoprotein and haptoglobin levels were also significantly increased postoperatively in all patients; however, they were significantly lower in pretreated patients. In conclusion, perioperative treatment with naproxen plus famotidine was well tolerated and reduced the acute phase response after instrumented spinal surgery. However, further research is needed to determine the best dose and timing of preoperative treatment administration, and to correlate these changes with long-term clinical results.

The curcuma antioxidants: pharmacological effects and prospects for future clinical use. A review.

In agreement with the predictions of the oxygen-stress theory of aging and age-related degenerative diseases, diet supplementation with a number of phenolic or thiolic antioxidants has been able to increase the life span of laboratory animals, protect against senescent immune decline and preserve the respiratory function of aged mitochondria. In addition to the above, more recent data reviewed here suggest that the polyphenolic compound curcumin and related non-toxic antioxidants from the rhizome of the spice plant Curcuma longa have a favorable effect on experimental mouse tumorigenesis as well as on inflammatory processes such as psoriasis and ethanol-caused hepatic injury. Our own research has focused on the effects of diet supplementation with an antioxidant-rich hydroalcoholic extract of the curcuma rhizome on key risk factors of atherogenesis and related cardiovascular disease. Our reviewed data show that, in human healthy subjects, the daily intake of 200 mg of the above extract results in a decrease in total blood lipid peroxides as well as in HDL and LDL-lipid peroxidation. This anti-atherogenic effect was accompanied by a curcuma antioxidant-induced normalization of the plasma levels of fibrinogen and of the apo B/apo A ratio, that may also decrease the cardiovascular risk. The reviewed literature indicates that curcumin and related plant co-antioxidants are powerful anti-inflammatory agents. Further, since they potentiate the anti-atherogenic effect of alpha-tocopherol, more extensive clinical testing of their probable usefulness in cardiovascular risk reduction seems justified.

[Colonoscopic follow-up of patients undergoing curative resection of colorectal cancer]. / Seguimiento colonoscópico de los pacientes intervenidos de carcinoma colorrectal con intención curativa.

AIM: To investigate the role of colonoscopy in the follow-up of patients undergoing curative resection of colorectal cancer. MATERIAL AND METHODS: A prospective study was performed of 102 patients with colorectal cancer who underwent surgery with curative intention. Postoperative colonoscopic follow-up was a minimum of 5 years. RESULTS: There were 62 males and 40 females. The mean duration of follow-up was 73.4 months. Synchronous polyps were found in 44.1% (114 in 45 patients) and metachronous polyps in 33.4% (64 in 34 patients). Synchronous carcinoma was detected in 7.8% (9 in 8 patients), metachronous carcinoma in 1.9% (2 in 2 patients) and suture recurrence in 4.9% (5 in 5 patients). Metachronous polyps developed in 55.5% of the patients with synchronous polyps and in only 15.8% of those with no synchronous polyps (p < 0.00005); the odds ratio was 6.67. Colonoscopy diagnosed 92 synchronous polyps and 64 metachronous polyps; of these, 34 were found to be significant(in 22 patients). Colonoscopy diagnosed 5 synchronous carcinomas; in 3 of these (polyps with non-invasive carcinoma) polypectomy constituted definitive therapy and in the remaining 2, curative resection was achieved. Colonoscopy diagnosed 2 stage C2 metachronous carcinomas at 63 and 94 months. Curative resection was achieved in both cases. Colonoscopic follow-up diagnosed 2 suture recurrences and resection was potentially curative. CONCLUSIONS: Colonoscopy was found to play an essential role in 30% of the patients. The technique allowed the early diagnosis of synchronous carcinomas and curative treatment of metachronous carcinomas and demonstrated that the presence of synchronous polyps increases the risk of developing metachronous polyps.