Clinical Cysticercosis epidemiology in Spain based on the hospital discharge database: What's new?

BACKGROUND: Cysticercosis (CC) is a tissue infection caused by the larval cysts of the pork tapeworm Taenia solium. It is usually acquired by eating contaminated food or drinking water. CC Cysts can develop in the muscles, the eyes, the brain, and/or the spinal cord. T. solium is found worldwide, but its prevalence has decreased in developed countries due to stricter meat inspection and better hygiene and sanitation. Nevertheless, CC is still a leading cause of seizures and epilepsy. In Spain, The disease is not nationally reportable and data on CC infected animals are also missing, despite the European Directive 2003/99/EC. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective descriptive study using the Spanish Hospitalization Minimum Data Set (CMBD). Data with ICD-9 CM cysticercosis code ("123.1") placed in first or second diagnostic position from 1997 to 2014 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed. A total of 1,912 hospital discharges with clinical cysticercosis were identified. From 1998 to 2008, an increasing trend in the number of CC hospitalizations was observed, decreasing afterwards, in parallel with a decrease in the external migration rate. The Murcia region had the highest median hospitalization rate (13.37 hospitalizations/100,000 population), followed by Navarra and Madrid. The 16-44 age group was the most represented (63.6%). The three most frequent associated diagnoses were epilepsy and convulsions (49.5%), hydrocephalus (11.8%) and encephalitis/myelitis/meningitis (11.6%). CONCLUSIONS/SIGNIFICANCE: There is a need for a common strategy on data collection, monitoring and reporting, which would facilitate a more accurate picture on the CC epidemiological scenario. Even if most cases might be imported, improving the human and animal CC surveillance will result useful both in gaining extended disease knowledge and reducing morbidity and related-costs.The authors received no specific funding for this work.S

Role of caveolin 1 on liver regeneration after partial hepatectomy. Mechanisms of signalling and effect on the regulation of hepatocyte proliferation

[ES]: Las caveolas participan en múltiples procesos celulares tales como el transporte vesicular, homeostasis del colesterol, regulación de la señalización intracelular, por integrinas y proliferación celular. Sin embargo, su función en el hígado no está bien establecida. La expresión de caveolina 1 (Cav), la proteína más abundante en las caveolas, está bien descrita en el hígado y en varias líneas de hepatocitos y en hígado cirrótico humano y en carcinoma hepatocelular. Sin embargo, el papel de Cav-1 en la fisiopatología hepática es controvertido, ya que se ha propuesto un papel crítico en el proceso de regeneración tras hepatectomía parcial (HP). Contrariamente a esta observación, nuestros datos sugieren que Cav-1 aumenta en el hígado regenerante, con una re-distribución de la proteína desde las caveolas hacia dominios no caveolares. Además, la Cav-1 localizada en estas fracciones está fosforilada en la tirosina 14. A pesar de ello, el gen de la Cav-1 es dispensable para la regeneración hepática tras HP, tal como se deduce de animales que carecen de este gen. En conjunto, estos datos muestran un papel dinámico de la Cav-1 en la proliferación hepática tras HP y en líneas hepáticas en cultivo, pero con mínimas implicaciones en el proceso regenerativo.[EN]: Although caveolae participate in many cellular processes such as vesicular transport, cholesterol homeostasis, regulation of signal transduction, integrin signaling and cell growth, their role in liver remains elusive. Expression of caveolin 1 (Cav), the most abundant protein of caveolae, has been reported in liver and in different hepatocyte cell lines, in human cirrhotic liver and in hepatocellular carcinomas. However, the role of Cav-1 in liver pathophysiology remains controversial and a critical role in regeneration after partial hepatectomy (PH) has been reported. Opposite to this observation, our data support the view that Cav-1 increases in liver after PH with a redistribution of the protein from the caveolae enriched domain to the noncaveolar fraction. Moreover, the Cav-1 located in the noncaveolar fraction is phosphorylated in tyrosine 14 (Tyr14). Even though, the Cav-1 gene is dispensable for liver regeneration after PH as deduced from data obtained with commercially available animals lacking this gene. Taken together these results support a dynamic role for Cav-1 in liver proliferation both in vivo after PH, and in vitro in cultured hepatic cell lines, but with minimal implications in the liver regeneration process.Peer Reviewe

Molecular markers in plasmodium falciparum linked to resistance to anti-malarial drugs in samples imported from Africa over an eight-year period (2002-2010): impact of the introduction of artemisinin combination therapy

BACKGROUND: Drug resistance is a major problem to control Plasmodium falciparum infection in endemic countries. During last decade, African countries have changed first-line treatment to artemisinin-based combinations therapy (ACT); sulphadoxine-pyrimethamine (SP) is recommended for Intermittent Preventive Therapy (IPT). Molecular markers related to P falciparum resistance were analysed for the period of transition from SP to ACT, in isolates imported from Africa. METHODS: A first group of samples was taken in the period between June 2002 and June 2006 (n = 113); a second group in the period between November 2008 and August 2010 (n = 46). Several alleles were analysed by nested PCR-RFLP: 51, 59, 108, 164, in the pfdhfr gene; 436, 437, 540, 581, in the pfdhps gene; 86, 1246, in the pfmdr1 gene and 76, in the pfcrt gene. The prevalence of alleles in the groups was compared with the chi-squared or Fisher's exact tests. RESULTS: The pfdhfr N51I, C59R and S108N were over to 90% in the two groups; all samples had the I164. In the pfdhps, 437 G and 581 G, increased up to 80% and 10.9% (p = 0.024), respectively in the second group. The 540 G decreases (24% to 16.%) and the 436A disappears at the end of the follow-up (p = 0.004) in the second group. The 76I-pfcrt stayed over 95% in the two groups. Prevalence of 86Y-pfmdr1 decreased over eight years. CONCLUSIONS: Pharmacological pressure affects the resistance strains prevalence. As for SP, the disappearance of 436A and the decrease in 540 G suggest that these mutations are not fixed. On the other hand, studies carried out after ACT introduction show there was a selection of strains carrying the SNPs N86Y, D1246Y in pfmdr1. In this work, the prevalence of pfmdr1- D1246Y is increasing, perhaps as a result of selective pressure by ACT. Continued surveillance is essential to monitor the effectiveness of treatments.S

Biomarkers in ocular chronic graft versus host disease: tear cytokine- and chemokine-based predictive model.

Producción CientíficaPurpose: To develop a tear molecule level-based predictive model based on a panel of tear cytokines and their correlation with clinical features in ocular chronic graft versus host disease (cGVHD). Methods: Twenty-two ocular cGVHD patients and 21 healthy subjects were evaluated in a controlled environmental research laboratory (CERLab). Clinical parameters were recorded, and tears were collected. Levels of 15 molecules (epidermal growth factor [EGF], IL receptor antagonist [IL-1Ra], IL-1β, IL-2, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-17A, interferon inducible protein [IP]-10/CXCL10, IFN-γ, VEGF, TNF-α, eotaxin 1, and regulated on activation normal T cell expressed and secreted [RANTES]) were measured by multiplex-bead assay and correlated with clinical parameters. Logistic regression was used to develop a predictive model. Leave-one-out cross-validation was applied. Classification capacity was evaluated in a cohort of individuals with dry eye (DE) of other etiologies different from GVHD. Results: Epidermal growth factor and IP-10/CXCL10 levels were significantly decreased in ocular cGVHD, positively correlating with tear production and stability and negatively correlating with symptoms, hyperemia, and vital staining. Interleukin-1Ra, IL-8/CXCL8, and IL-10 were significantly increased in ocular cGVHD, and the first two correlated positively with symptoms, hyperemia, and ocular surface integrity while negatively correlating with tear production and stability. Predictive models were generated, and the best panel was based on IL-8/CXCL8 and IP-10/CXCL10 tear levels along with age and sex, with an area under the receiving operating curve of 0.9004, sensitivity of 86.36%, and specificity of 95.24%. Conclusions: A predictive model based on tear levels of IL-8/CXCL8 and IP-10/CXCL10 resulted in optimal sensitivity and specificity. These results add further knowledge to the search for potential biomarkers in this devastating ocular inflammatory disease.Ministry of Economy and Competitiveness, Madrid, Spain, SAF-2010 15631 (AES)

Characterization of the Plasmodium falciparum sarcoplasmic/endoplasmic reticulum Ca2+-ATPase gene in samples from Equatorial Guinea before implementation of artemisinin-based combination therapy

Plasmodium falciparum resistance to the primary drugs used for treatment of malaria has become the main obstacle to malaria control. Artemisinin combination therapies are the current treatment strategy, and it has been suggested that resistance to artemisinin derivatives may be related to mutations in the Plasmodium falciparum sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase ortholog of the mammalian sarco-endoplasmic reticulum Ca(2+) ATPase gene, known as the pfatp6 gene. Thus, the purpose of this study was to determine the prevalence of single-nucleotide polymorphisms (SNPs) in pfatp6. The presence of different SNPs was detected by polymerase chain reaction amplification of the pfatp6 gene, and then sequencing to identify all possible alleles of the gene. A total of 20 SNPs were detected, including eight SNPs that have not been previously described: K481R in Malabo; R801H on Annobon Island; and the synonymous SNPs a141t, c1788t, a2211g, t2739g, a2760c, and g2836a. The genotypic profile of pfatp6 in samples from Equatorial Guinea, may be a useful epidemiologic tool for monitoring local efficacy of artemisinin combination therapies.This study was supported by the Spanish Agency for International Development Cooperation and the Collaborative Research Network in Tropical Diseases.S

Age and sex-adjusted reference intervals in tear cytokine levels in healthy subjects

Producción CientíficaAlterations in tear cytokine levels have been associated with various ocular disorders as compared to those in healthy subjects. However, age and sex are not always considered in these comparisons. In this study we aimed to establish age and sex reference intervals (RIs) for tear cytokine levels in healthy people. Tear samples were taken from 75 males and 82 females, aged 18–88 years, and tear cytokine levels were determined. Age- and sex-adjusted RIs for epidermal growth factor (EGF), fractalkine, interleukin (IL)-1 receptor antagonist (RA), IL-7, IL-8, interferon inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, and vascular endothelial growth factor (VEGF) tear cytokine levels in a healthy sample were established using generalized additive for location, scale and shape (GAMLSS) models. RIs were tested in two external samples: a validation sample of 40 individuals with normal results at four Dry Eye Disease (DED) clinical diagnostic tests (OSDI, T-BUT, corneal staining and Schirmer test); and a utility sample of 13 severe DED cases. IL-1RA, IL-8, IP-10, and MCP-1 levels showed a positive association with age, while EGF was negatively correlated. IL-7 concentration increased up to 40 years and again after 70 years, observing a quasi-linear decrease between them. For VEGF, higher levels were observed in the middle-aged range. Regarding sex-influence, fractalkine tear levels were higher in men, whereas those of IL-7, IL-8, and IP-10 were higher in women. Using the estimated age- and sex-adjusted RIs, more than 92% of the validation sample was correctly classified, and 100% of the severe DED patients in the utility sample had concentrations outside the RIs in at least two of the cytokines evaluated

Epigenetic Landscape in Blood Leukocytes Following Ketosis and Weight Loss Induced by a Very Low Calorie Ketogenic Diet (VLCKD) in Patients With Obesity

[Abstract] Background:The molecular mechanisms underlying the potential health benefits of a ketogenic diet areunknown and could be mediated by epigenetic mechanisms.Objective:To identify the changes in the obesity-related methylome that are mediated by the inducedweight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenicdiet (VLCKD).Methods:Twenty-one patients with obesity (n¼12 women, 47.9±1.02 yr, 33.0±0.2 kg/m2) after 6months on a VLCKD and 12 normal weight volunteers (n¼6 women, 50.3±6.2 yrs, 22.7±1.5 kg/m2)were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes wereobtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD(n¼10) and at baseline in volunteers (n¼12). Results were further validated by pyrosequencing inrepresentative cohort of patients on a VLCKD (n¼18) and correlated with gene expression.Results:After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes).The VLCKD altered methylation levels in patients with obesity had high resemblance with those fromnormal weight volunteers and was concomitant with a downregulation of DNA methyltransferases(DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein meta-bolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoringassociated events were identified, includingZNF331,FGFRL1(VLCKD-induced weight loss) andCBFA2T3,C3orf38,JSRP1, andLRFN4(VLCKD-induced ketosis). Interestingly,ZNF331andFGFRL1were validated inan independent cohort and inversely correlated with gene expression.Conclusions:The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive ofnormal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss.This work was supported by the PronoKal Group® and grants from the Fondo de Investigacion Sanitaria as well as PI17/01287, PI20/00628 and PI20/00650 research projects and CIBERobn from the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigación; Fondo Europeo de Desarrollo Regional (FEDER) Ana B Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII, co-financed by the European Regional Development Fund (FEDER) and Xunta de Galicia-GAIN (IN607B2020)Xunta de Galicia; IN607B202