Pandemic influenza in a southern hemisphere setting: the experience in Peru from May to September, 2009

This paper presents a description of Peru’s experience with pandemic H1N1 influenza 2009. It is based on data from four main surveillance systems: a) ongoing sentinel surveillance of influenza-like illness cases with virological surveillance of influenza and other respiratory viruses; b) sentinel surveillance of severe acute respiratory infections and associated deaths; c) surveillance of acute respiratory infections in children under the age of five years and pneumonia in all age groups; and d) case and cluster surveillance. On 9 May 2009, the first confirmed case of pandemic H1N1 influenza in Peru was diagnosed in a Peruvian citizen returning from New York with a respiratory illness. By July, community transmission of influenza had been identified and until 27 September 2009, a total of 8,381 cases were confirmed. The incidence rate per 10,000 persons was 4.4 (in the 0–9 year-olds) and 4.1 (in the 10–19 year-olds). During epidemiological weeks (EW)* 26 to 37, a total of 143 fatal cases were notified (a case fatality of 1.71%, based on confirmed cases). The maximum peak in the number of cases was reached in EW 30 with 37 deaths. Currently, the impact of the pandemic in the Peruvian population has not been too severe, and fortunately, healthcare centres have not been overwhelmed. However, the future of this pandemic is uncertain and despite the fact that our country has not been seriously affected, we should be prepared for upcoming pandemic waves

Relaciones entre el recuento de células somáticas, test de mastitis California, conductividad eléctrica y el diagnóstico de mastitis subclínicas en cabras lecheras

En el tambo caprino, las mastitis son un problema sanitario mayor que afecta tanto la productividad como la inocuidad y calidad de los productos. Debido a que el diagnóstico de las mastitis subclínicas plantea problemas para su correcto monitoreo, el objetivo planteado fue analizar las relaciones entre el estado infeccioso de las mamas, los diferentes métodos de diagnóstico como el conteo de células somáticas (CCS), test de mastitis California (CMT) y la conductividad eléctrica (CE) y sus relaciones y posibilidades de aplicación en las condiciones de los tambos caprinos del país. A partir de cabras, mayormente Saanen (71,9%) en ordeño en los períodos sept/2010-mar/2011 y jun/2011-dic/2011, se tomaron mensualmente muestras de leche individuales (n=846) de cada medio mamario. El estado infeccioso de cada muestra se determinó por cultivos bacterioló- gicos dividiéndolo en medios mamarios no infectados (NI), infectados con patógenos menores y patógenos mayores. El CCS se realizó por Fossomatic, y a modo de control por microscopía directa mediante técnicas de Breed clásica y método de Verde metil Y pironina (VMYP). La pruebas de conductividad eléctrica (CE) se realizaron por dispositivo manual y el CMT fue el clásico. Además, con sólo 30 muestras se evaluó un test comercial “PortaSCC goat” para leche caprina. Las relaciones entre variables fueron analizadas por correlación lineal y regresión simple y sus diferencias por Chi cuadrado o análisis de varianza. Se calculó la sensibilidad (S) y la especificidad (E) y los valores predictivos (VP) de las pruebas. Como patógenos menores se aislaron Staphylococcus sp. coagulasa negativo, SCN (n=37) y como patógenos mayores sólo Staphylococcus aureus (n=13). La presencia de patógenos elevó los CCS (P<0001) y los CMT (P<0,0001), pero no la CE (0,09). Las medias de los CCS para NI, SCN y S. aureus fueron respectivamente de 789427±1139886, 1891432±1521385 y 5296615±3806640. La correlación hallada entre el CCS y de la CE con el estado sanitario de los medios mamarios fue respectivamente de r=0,41 (P<0.0001) y de r=0,12 (P<0,03). El CCS tuvo una correlación de r=0,86 (p<0,0001) con el VMYP, de r=0,64 (p<0,0001) con el CMT, de r=0,24 (p<0,0001) con la CE y de 0,47 (p<0,009) con el PortaSCC. El VMYP dio un conteo celular de un 20,8% inferior al Breed. Los CMT 0, T, 1, 2, y 3 se correspondieron a CCS medios respectivos de 326823, 494294, 741670, 1680557 y 3842440. La S y E respectivamente fueron de 70% y 79% para CCS, del 68% y 80% para el CMT y de solo 58% y 60% para la CE. El estudio muestra que tanto el CCS (línea de corte <1000000) como el CMT (0, T, 1) pueden ser usados para monitorear la presencia de mastitis subclínicas, teniendo en cuenta que presentan una E buena y alto VP negativo (98%) para el diagnóstico de ubres sanas y una S aceptable para detectar infecciones (especialmente patógenos mayores), siempre que se tengan en cuenta el diagnóstico bacteriológico, la recurrencia de los diagnósticos y otros factores no infecciosos ligados al aumento del CCS en las cabras.Mastitis in udders is a major health problem, affecting productivity, safety and product quality in the dairy goat. Because the diagnosis of subclinical mastitis is problematic for accurate monitoring, the objective of this study is to evaluate the relationships among the infectious status of half udder and different diagnosis methods: somatic cell count (SCC), California mastitis test (CMT) and electric conductivity (CE) and its diagnostic possibilities in the real dairy goat systems. From milked goats (Saanen, 76%) during Sept/2010-March/2011 and June/2011-Dec/2011 periods, monthly samples (n=846) of milk were taken from each half udder. Udder halves infectious status was assessed by bacteriological cultures and classified in three groups: negative culture (NI), and intrammary infections by minor pathogens and by major pathogens. Chi square, analysis of variance and correlation and regression analysis were carried out to analyse interrelations between variables. Sensitivity (S), specificity (SP) and predictive values (VP) were calculated. Coagulase-negative Staphylococcus sp SCN (n=37), were the minor pathogen and Staphylococcus aureus (n=13), was the only major pathogen isolated. Pathogen increase CCS (P<0001) and CMT (P<0.0001) but not CE (0.09). The average values for CCS of NI, SCN y S. aureus were respectively 789427±1139886, 1891432±1521385 y 5296615±3806640. The correlation obtained between CCS and CE was respectively r=0.41 (P<0.0001) and r=0.12 (P<0,03). The CCS had significative (p<0.0001) correlations of r=0.86 with VMYP, r=0.64 with CMT, r=0.24 with CE and 0.47 with PortaSCC. The VMYP cell counts was 20.8% lesser than Breed counts. CCS averages were for the CMT scores of 326823 (0), 494294 (traces), 741670 (1), 1680557 (2) and 3842440 (3) cells/ml. S and SP were of 70% and 79% for CCS, 68% and 80% for CMT and 58% y 60% for CE respectively. The study shows that both the CCS (cut line <1000000) and CMT (0, T, 1) can be used to monitor the presence of subclinical mastitis, considering that exhibit good high negative VP (98% ) and good SP for the diagnosis of healthy udders and acceptable S for infections (specially major pathogens), provided that the bacteriological diagnosis, recurrence of diagnosis and other no infectious factors associated to elevated CCS are taken into account.EEA SaltaFil: Suarez, Victor Humberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Martinez, Gabriela Marcela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Gianre, Vilma Rita. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Calvinho, Luis Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Rachoski, A. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Chávez, M. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Salatin, Antonio Omar. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Orozco, S. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Sánchez, V. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Bertoni, Emiliano Agustí­n. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; Argentin

Hospital-based proton therapy implementation during the COVID pandemic: early clinical and research experience in a European academic institution

Introduction A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efcient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. Methods A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities’ recommendations. The temporary trends of patients care and research projects proposals were registered. Results 3 out of 14 members of the professional staf involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientifc production was adapted to the pandemic evolution and its infuence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. Conclusions Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefts of online learning will shape the future of proton therapy education

Down-Regulation of miR-101 in Endothelial Cells Promotes Blood Vessel Formation through Reduced Repression of EZH2

Angiogenesis is a balanced process controlled by pro- and anti-angiogenic molecules of which the regulation is not fully understood. Besides classical gene regulation, miRNAs have emerged as post-transcriptional regulators of angiogenesis. Furthermore, epigenetic changes caused by histone-modifying enzymes were shown to modulate angiogenesis as well. However, a possible interplay between miRNAs and histone-modulating enzymes during angiogenesis has not been described. Here we show that VEGF-mediated down-regulation of miR-101 caused pro-angiogenic effects. We found that the pro-angiogenic effects are partly mediated through reduced repression by miR-101 of the histone-methyltransferase EZH2, a member of the Polycomb group family, thereby increasing methylation of histone H3 at lysine 27 and transcriptome alterations. In vitro, the sprouting and migratory properties of primary endothelial cell cultures were reduced by inhibiting EZH2 through up-regulation of miR-101, siRNA-mediated knockdown of EZH2, or treatment with 3-Deazaneplanocin-A (DZNep), a small molecule inhibitor of EZH2 methyltransferase activity. In addition, we found that systemic DZNep administration reduced the number of blood vessels in a subcutaneous glioblastoma mouse model, without showing adverse toxicities. Altogether, by identifying a pro-angiogenic VEGF/miR-101/EZH2 axis in endothelial cells we provide evidence for a functional link between growth factor-mediated signaling, post-transcriptional silencing, and histone-methylation in the angiogenesis process. Inhibition of EZH2 may prove therapeutic in diseases in which aberrant vascularization plays a role

Correlation of Serotype-Specific Dengue Virus Infection with Clinical Manifestations

Dengue virus (DENV) causes disease in millions of people annually and disproportionately affects those in the developing world. DENVs may be divided into four serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) and a geographical region may be affected by one or more DENV serotypes simultaneously. Infection with DENV may cause life-threatening disease such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), but more often causes less severe manifestations affecting a wide range of organs. Although many previous reports have explored the role of the different DENV serotypes in the development of severe manifestations, little attention has focused on the relative role of each DENV serotype in the development of cutaneous, respiratory, gastrointestinal, musculoskeletal, and neurological manifestations. We recruited a large group of participants from four countries in South America to compare the prevalence of more than 30 manifestations among the four different DENV serotypes. We found that certain DENV serotypes were often associated with a higher prevalence of a certain manifestation (e.g., DENV-3 and diarrhea) or manifestation group (e.g., DENV-4 and cutaneous manifestations)

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium

10.1186/bcr3381Breast Cancer Research15

Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium.</p> <p>Methods</p> <p>CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in <it>ADH1C</it>, <it>APC</it>, <it>CCDN1</it>, <it>IL6</it>, <it>IL8</it>, <it>IRS1</it>, <it>MTHFR</it>, <it>PPARG</it>, <it>VDR </it>and <it>ARL11</it>, and 18 selected variants in the mucin gene family.</p> <p>Results</p> <p>None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a <it>P</it>-value < 0.05 in EPICOLON stage 1 [rs698 in <it>ADH1C </it>(OR = 1.63, 95% CI = 1.06-2.50, <it>P</it>-value = 0.02, recessive), rs1800795 in <it>IL6 </it>(OR = 1.62, 95% CI = 1.10-2.37, <it>P</it>-value = 0.01, recessive), rs3803185 in <it>ARL11 </it>(OR = 1.58, 95% CI = 1.17-2.15, <it>P</it>-value = 0.007, codominant), and rs2102302 in <it>GALNTL2 </it>(OR = 1.20, 95% CI = 1.00-1.44, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, <it>P</it>-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, <it>P</it>-value = 0.09, log-additive 0, 1, 2 alleles).</p> <p>Conclusions</p> <p><it>ARL11</it>, <it>ADH1C</it>, <it>GALNTL2 </it>and <it>IL6 </it>genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.</p

Arboviral Etiologies of Acute Febrile Illnesses in Western South America, 2000–2007

Over recent decades, the variety and quantity of diseases caused by viruses transmitted to humans by mosquitoes and other arthropods (also known as arboviruses) have increased around the world. One difficulty in studying these diseases is the fact that the symptoms are often non-descript, with patients reporting such symptoms as low-grade fever and headache. Our goal in this study was to use laboratory tests to determine the causes of such non-descript illnesses in sites in four countries in South America, focusing on arboviruses. We established a surveillance network in 13 locations in Ecuador, Peru, Bolivia, and Paraguay, where patient samples were collected and then sent to a central laboratory for testing. Between May 2000 and December 2007, blood serum samples were collected from more than 20,000 participants with fever, and recent arbovirus infection was detected for nearly one third of them. The most common viruses were dengue viruses (genera Flavivirus). We also detected infection by viruses from other genera, including Alphavirus and Orthobunyavirus. This data is important for understanding how such viruses might emerge as significant human pathogens