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Protein-ligand interactions are essential to drug discovery and drug development efforts. Desirable on-target or multitarget interactions are the first step in finding an effective therapeutic, while undesirable off-target interactions are the first step in assessing safety. In this work, we introduce a novel ligand-based featurization and mapping of human protein pockets to identify closely related protein targets and to project novel drugs into a hybrid protein-ligand feature space to identify their likely protein interactions. Using structure-based template matches from PDB, protein pockets are featured by the ligands that bind to their best co-complex template matches. The simplicity and interpretability of this approach provide a granular characterization of the human proteome at the protein-pocket level instead of the traditional protein-level characterization by family, function, or pathway. We demonstrate the power of this featurization method by clustering a subset of the human proteome and evaluating the predicted cluster associations of over 7000 compounds.
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Proteoma , Humanos , Ligação Proteica , Sítios de Ligação , Conformação Proteica , Ligantes , Análise por ConglomeradosRESUMO
BACKGROUND: The presence of toxic metals in human populations is strongly associated with chronic diseases. AIM: To determine levels of lead, chromium, cadmium, mercury and inorganic arsenic (AsIn) in the general population aged over 5 years in Antofagasta, Chile. MATERIAL AND METHODS: People living in Urban Antofagasta for at least five years were considered eligible. Biological samples were obtained to measure heavy metals. RESULTS: One thousand two hundred three participants with a median age of 43 years (656 women) were studied. Their mean time of residence in the city was 30 years, and 52% smoked. Eight percent of the adult population and 12% of children had AsIn values above 35 µg/L, while 75% of the population had levels below 21.9 µg/L. The other metals were below the risk levels defined by the health authority (10 µg/L for chromium, 10 µg/L for mercury, 2 µg/L for cadmium, 5 and 10 µg/dL for blood lead for children and adults, respectively). The factors associated with high levels of AsIn in adults were male sex, living more than 200 meters from monitoring points, and low schooling. In children, the associated variables were high intake of seafood products and having a caregiver with less than 8 years of schooling. Contrary to expectations, the greatest risk of presenting altered levels of the metals occurred in the population living more than 500 meters from the identified risk sources (90% of the population). CONCLUSIONS: The findings of this study suggest that all potential sources of exposure to AsIn should be evaluated, and surveillance actions should be established to reduce involuntary exposure to this metalloid.
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Chumbo/sangue , Metais Pesados/urina , Adulto , Chile/epidemiologia , Monitoramento Ambiental , Feminino , Humanos , MasculinoRESUMO
Leptospirosis, a bacterial infection transmitted through contact with infected animals or contaminated water sources, imposes a substantial health burden in Colombia. Since 2007, the National Institute of Health (INS) has mandated the notification and confirmation of all suspected leptospirosis cases. This passive surveillance program employs the microscopic agglutination test (MAT) on serum samples to ascertain confirmed cases of leptospirosis infection. However, the absence of a robust surveillance system has hindered our comprehensive understanding of the morbidity, mortality, geographical distribution, species/serovars, and strains responsible for severe disease. Our study aimed to provide an epidemiological overview of MAT-confirmed human leptospirosis cases reported over 6 years (2015-2020) in Colombia. In addition, we offer insights into the status of leptospirosis in the country, focusing on risk factors and proposing potential improvements for diagnosis and disease management. During the 6-year surveillance period, the laboratory at the INS received 3,535 serum samples from suspected human leptospirosis cases, with 880 (25%) confirmed through MAT. The incidence of leptospirosis was calculated at 1.9 cases per 100,000 people, with a higher prevalence among men (82.1%). Furthermore, 54 (6.1%) deaths were confirmed as leptospirosis, and cases were documented across nearly all regions of Colombia. Our findings emphasize the urgent need to strengthen leptospirosis laboratory surveillance, implement effective prevention measures, and enhance diagnostic capabilities in Colombia. The analysis conducted in this study provides the groundwork for estimating the impact of leptospirosis and raises awareness of its significance in public health.
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Chagas disease (CD) is a neglected parasitic zoonotic disease that affects over 6 million people worldwide. We conducted a retrospective study to analyze the spatiotemporal trends and risk factors for hospitalization rates of CD with cardiac and digestive diagnoses in Chile. We used the Mann-Kendall analysis for temporal trends, Global Moran's Index, and Local Indicators of Spatial Association to identify spatial autocorrelation, and regression models to determine the risk factors associated with in-hospital mortality and surgical intervention. Between 2010 and 2020, a total of 654 hospitalizations were reported, corresponding to 527 individuals. The hospitalization rate steadily decreased over the years (t = -0.636; p = 0.009). The Global Moran's I for the study period showed a positive spatial autocorrelation for hospitalization municipality and for residence municipality of CD patients (I = 0.25, p<0.001 and I = 0.45, p<0.001 respectively), indicating a clustering of hospitalizations in northern municipalities. The most frequent diagnosis was a chronic CD with digestive system involvement (55.8%) followed by a chronic CD with heart involvement (44.2%). The highest percentage of hospital discharges was observed among males (56.9%) and in the 60-79 age group (52.7%). In-hospital mortality risk was higher with increasing age (OR = 1.04), and in patients with cardiac involvement (OR = 2.3), whereas factors associated with the risk of undergoing a surgical intervention were sex (OR = 1.6) and diagnosis of CD with digestive involvement (OR = 4.4). The findings of this study indicate that CD is still a significant public health burden in Chile. Efforts should focus on improving access to timely diagnoses and treatment, reducing disease progression and hospitalization burden, and supporting clinicians in preventing complications and deaths.
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Doença de Chagas , Mortalidade Hospitalar , Hospitalização , Análise Espaço-Temporal , Humanos , Chile/epidemiologia , Masculino , Feminino , Doença de Chagas/mortalidade , Doença de Chagas/epidemiologia , Hospitalização/estatística & dados numéricos , Fatores de Risco , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Doença Crônica , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , CriançaRESUMO
BACKGROUND: Leptospirosis is a common zoonoses and is a major global public health threat. Most cases are mild, typically presenting as a non-specific acute febrile illness. However, leptospirosis can have life-threatening manifestations, including pulmonary hemorrhage syndrome, and acute kidney injury. In Colombia, notification and lab-confirmation of suspected human cases are mandatory. However, little is known about the demographic and clinical factors associated with severe leptospirosis, which could help to reduce clinical complications and mortality. Our aim was to identify risk factors associated with severe leptospirosis, intensive care unit (ICU) admission, and mortality in lab-confirmed cases in Colombia, 2015-2020. METHODS AND FINDINGS: We analyzed 201 lab-confirmed human leptospirosis cases by microagglutination test. We used a logistic regression to identify the demographic and clinical risk factors associated with severe leptospirosis, admission to ICU, and death. Most leptospirosis confirmed cases occurred in men (85.6%); the mean age was 36.7 years. We classified severe cases (43.3%) by clinical manifestations as renal (29.9%) and liver (27.4%) failure, multiple-organ failure (24.4%), septic shock (24.4%), Weil syndrome (18.4%), pulmonary hemorrhage (18.4%), and meningitis (2.5%), admitted to the ICU (30.3%), and fatal (8.5%). Clinical conditions associated with severe leptospirosis were dyspnea (OR: 5.54; 95% CI: 1.46 to 20.98), tachycardia (OR:9.69; 95% CI: 15.96 to 58.8), and rash (OR: 10.25; 95% CI: 25.01 to 42.08). CONCLUSIONS: We identified demographic characteristics and clinical symptoms associated with severe leptospirosis in Colombia. We hope these results can support clinicians in providing timely treatment to leptospirosis patients to avoid preventable medical complications or deaths.
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Leptospirose , Pneumopatias , Masculino , Animais , Humanos , Adulto , Colômbia/epidemiologia , Leptospirose/complicações , Leptospirose/epidemiologia , Leptospirose/diagnóstico , Hemorragia , Síndrome , Fatores de Risco , DemografiaRESUMO
Minimizing the human and economic costs of the COVID-19 pandemic and future pandemics requires the ability to develop and deploy effective treatments for novel pathogens as soon as possible after they emerge. To this end, we introduce a new computational pipeline for the rapid identification and characterization of binding sites in viral proteins along with the key chemical features, which we call chemotypes, of the compounds predicted to interact with those same sites. The composition of source organisms for the structural models associated with an individual binding site is used to assess the site's degree of structural conservation across different species, including other viruses and humans. We propose a search strategy for novel therapeutics that involves the selection of molecules preferentially containing the most structurally rich chemotypes identified by our algorithm. While we demonstrate the pipeline on SARS-CoV-2, it is generalizable to any new virus, as long as either experimentally solved structures for its proteins are available or sufficiently accurate predicted structures can be constructed.
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BACKGROUND: Leptospirosis is a zoonosis endemic in some regions in Chile. Since its inclusion into the list of notifiable diseases, the Chilean Ministry of Health was able to maintain an adequate surveillance of leptospirosis. Nonetheless, some cases are not reported due to subclinical disease or nonspecific symptoms. OBJECTIVES: Determine the national prevalence of leptospirosis and assess the epidemiological characteristics of seropositive individuals. METHODS: Secondary data analysis of the National Health Survey, 2003. RESULTS: National prevalence was 0.4%. Low socioeconomical status and female gender were characteristics, which were more frequently found in sero-positive cases. The most common serovars were icterohaemorrhagiae, bratislava and pomona. CONCLUSION: We present the first epidemiological analysis of leptospirosis on a national level in Chile. Thus, the study contributes to the knowledge the epidemiological situation of this disease in Chile.
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Leptospirose/epidemiologia , Adolescente , Adulto , Criança , Chile/epidemiologia , Métodos Epidemiológicos , Feminino , Humanos , Leptospira/classificação , Leptospirose/microbiologia , Masculino , Pessoa de Meia-Idade , Terapia Socioambiental , Adulto JovemRESUMO
UNLABELLED: During year 2011 two outbreaks of Salmonella infection captured media attention in the Metropolitan Area (MA) in Chile: one of typhoid fever associated to Salmonella serotype Typhi, and the other, of gastroenteritis related to Salmonella serotype Enteritidis, both with decreasing or stable rates in the previous years. The aim of this work is to analyze probable causes of their reemergence. METHODS: Several government websites were searched looking for epidemiological data. RESULTS: Typhoid fever rates have declined to current values of 1 case per 100.000 habitants, a decreased associated to improvements in the human development index. The typhoid outbreak was associated to a predominant clone within the MA. The only risk factor identified was consumption of raw vegetables acquired in open fairs, but without identifying a common source. Despite improvements in disease notification and molecular epidemiology capabilities, this outbreak is coincidental with a reduced number of food inspection visits in the MA, probably explained by the limited personnel available for this task. In the case of Salmonella Enteritidis, rates have increased twice since 1998 (5.3 to 10.7 per 100.000 habitants) with an important increase in the number of outbreaks linked to this agent (7 to 31 annual outbreaks) since year 2005. Persistence of this problem is probably associated to the low surveillance of poultry farms made by the Chilean state, to the absence of a cold chain during collection, distribution and selling of eggs, and to the lack of an educational program directed to the population. The recent regulation that bans home-made mayonnaise in restaurant or fast food stores is an important advance that requires further evaluation. CONCLUSIONS: The persistence and reemergence of different kind of Salmonellosis in Chile suggests chronic problems on the size and role of the Chilean state regarding food safety.
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Surtos de Doenças , Manipulação de Alimentos/legislação & jurisprudência , Gastroenterite/epidemiologia , Intoxicação Alimentar por Salmonella/epidemiologia , Febre Tifoide/epidemiologia , Chile/epidemiologia , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Notificação de Doenças , Inocuidade dos Alimentos , Gastroenterite/microbiologia , Humanos , Incidência , Fatores de Risco , População UrbanaRESUMO
BACKGROUND: We developed an extendable open-source Loop-mediated isothermal AMPlification (LAMP) signature design program called LAVA (LAMP Assay Versatile Analysis). LAVA was created in response to limitations of existing LAMP signature programs. RESULTS: LAVA identifies combinations of six primer regions for basic LAMP signatures, or combinations of eight primer regions for LAMP signatures with loop primers, which can be used as LAMP signatures. The identified primers are conserved among target organism sequences. Primer combinations are optimized based on lengths, melting temperatures, and spacing among primer sites. We compare LAMP signature candidates for Staphylococcus aureus created both by LAVA and by PrimerExplorer. We also include signatures from a sample run targeting all strains of Mycobacterium tuberculosis. CONCLUSIONS: We have designed and demonstrated new software for identifying signature candidates appropriate for LAMP assays. The software is available for download at http://lava-dna.googlecode.com/.
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Alinhamento de Sequência/métodos , Análise de Sequência de DNA/métodos , Software , Sequência de Bases , Primers do DNA/genética , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e EspecificidadeRESUMO
Lockdown during the COVID-19 pandemic imposed changes in children's daily routine that could lead to changes in behavior patterns. Using a survey targeted at children under 17 years of age, we described dietary (adherence to Mediterranean diet, AMD) and sleeping habits (disorders of initiating and maintaining sleep) after the implementation of lockdown, and examined the probability of the inadequate frequency of physical activity (PA) and use of TV and electronic devices (TV-ED) before and after lockdown through generalized estimating equation models, accounting for age and gender differences. From 3464 children included, 53.2% showed optimal AMD; 79.2% referred to delayed bedtime; and 16.3% were suspected of sleeping disorders after the implementation of lockdown. Delay in bedtime was more frequent among children older than 6 years, and inadequate sleeping hours among those younger than 11 years. There were no gender differences in AMD or sleeping habits. The odds of inadequate frequency of PA and TV-ED use were greater after lockdown, with a greater risk for TV-ED use. Boys were at greater risk of inadequate PA frequency and TV-ED use. Odds ratio of inadequate PA was greater at older ages. Lockdown could influence changes in children's habits that could lead to risk factors for non-communicable diseases during adulthood if such behaviors are sustained over time.
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COVID-19/epidemiologia , Saúde da Criança , Hábitos , Doenças não Transmissíveis/epidemiologia , Pandemias , Obesidade Infantil/epidemiologia , SARS-CoV-2 , Adolescente , Criança , Pré-Escolar , Exercício Físico , Feminino , Humanos , Masculino , Espanha/epidemiologiaRESUMO
This study evaluated the preclinical effect of obesity on the ventricular remodeling in adolescents with morbid obesity, and determined if subjects labelled as metabolically healthy obesity (MHO) presented better heart index than those with metabolically unhealthy obesity (MUO). Prospective case-control research of 45 adolescents (14-year-old) with morbid obesity and 25 normal weight adolescents' gender- and age-matched with Tanner stage 4-5. Left ventricle (LV) was evaluated by conventional Doppler echocardiography, tissue Doppler imaging and two-dimensional speckle tracking echocardiography. Compared to normal-weight subjects, adolescents with morbid obesity presented a high percentage of pathological LV geometry (87%; p<0.01), and systolic and diastolic dysfunctions only detected by E/A ratio (2.0 vs 1.7, p<0.01), global longitudinal strain (-21.0% vs -16.5%, p<0.01), and early diastolic strain rate (3.2 vs 2.2, p<0.01). A correlation was found between impaired cardiac index and body mass index (BMI), high blood pressure, hyperglycemia, low HDL-cholesterol and hypertriglyceridemia. BMI and HDL-cholesterol were the most significant independent variables. No significant differences were found in structural and functional cardiac index when MHO and MUO subjects were compared (global longitudinal strain: -17.0% vs -16.4%, p0.79). Morbidly obese adolescents have an abnormal LV geometry, closely related to BMI, and systolic and diastolic LV dysfunctions. Adolescents labelled as MHO, despite exhibiting better BMI and insulin-resistance values, present the same pathological heart changes as MUO.
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Índice de Massa Corporal , Ecocardiografia Doppler/métodos , Ventrículos do Coração/diagnóstico por imagem , Obesidade Mórbida/complicações , Obesidade Infantil/complicações , Disfunção Ventricular Esquerda/etiologia , Adolescente , Criança , Diástole , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Fatores de Risco , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
A rapid response is necessary to contain emergent biological outbreaks before they can become pandemics. The novel coronavirus (SARS-CoV-2) that causes COVID-19 was first reported in December of 2019 in Wuhan, China and reached most corners of the globe in less than two months. In just over a year since the initial infections, COVID-19 infected almost 100 million people worldwide. Although similar to SARS-CoV and MERS-CoV, SARS-CoV-2 has resisted treatments that are effective against other coronaviruses. Crystal structures of two SARS-CoV-2 proteins, spike protein and main protease, have been reported and can serve as targets for studies in neutralizing this threat. We have employed molecular docking, molecular dynamics simulations, and machine learning to identify from a library of 26 million molecules possible candidate compounds that may attenuate or neutralize the effects of this virus. The viability of selected candidate compounds against SARS-CoV-2 was determined experimentally by biolayer interferometry and FRET-based activity protein assays along with virus-based assays. In the pseudovirus assay, imatinib and lapatinib had IC50 values below 10 µM, while candesartan cilexetil had an IC50 value of approximately 67 µM against Mpro in a FRET-based activity assay. Comparatively, candesartan cilexetil had the highest selectivity index of all compounds tested as its half-maximal cytotoxicity concentration 50 (CC50) value was the only one greater than the limit of the assay (>100 µM).
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In order to investigate the role of the nuclear factor kappaB (NFKB) pathway on gene expression in the eutopic endometrium in endometriosis, and in particular of interleukin-6 (IL6), we evaluated RELA, IkappaB kinase (CHUK), NFKBIA and IL6 expressions and NFKB DNA binding in eutopic endometrium from women with endometriosis. Eutopic endometrium was obtained from 37 women with endometriosis and 42 fertile women during laparoscopy. We analysed RELA, CHUK, NFKBIA and IL6 mRNA levels (RT-PCR); RELA, CHUK and NFKBIA proteins and p-NFKBIA/NFKBIA ratio (western blot); and NFKB binding (DNA shift assay) and IL6 concentration (ELISA) in endometrial explants. Our results indicate that mRNA and cytoplasmic proteins of RELA and CHUK exhibit constant levels in normal endometrium during the menstrual cycle. A dramatic increase (P<0.05) in NFKBIA mRNA expression, RELA nuclear presence and the mRNA and the protein of IL6 during late secretory phase was also observed in this tissue. By contrast, in eutopic endometrium from endometriosis patients, a decrease (P<0.05) in IL6 mRNA and protein (61%), NFKBIA mRNA (46%), p-NFKBIA/NFKBIA ratio (42%), RELA nuclear stromal (68%) and CHUK (48%) proteins were found exclusively during the late secretory phase compared with normal endometrium. In conclusion, the canonical activation of NFKB pathway is deregulated and may have reduced transcriptional function affecting NFKBIA and IL6 expression, genes related local proinflammatory processes. These molecular alterations observed during the late secretory phase in eutopic endometrium from endometriosis patients constitute a NFKB system dysfunction, suggesting that NFKB could be an important factor in endometriosis aetiology.
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Endometriose/metabolismo , Endométrio/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Adulto , Estudos de Casos e Controles , DNA/metabolismo , Feminino , Humanos , Quinase I-kappa B/metabolismo , Proteínas I-kappa B/metabolismo , Inibidor de NF-kappaB alfa , RNA Mensageiro/metabolismo , Adulto JovemRESUMO
Cystic echinococcosis is a chronic parasitic zoonosis of high prevalence in Chile. We report a clinical case of a 66-year-old man, domiciled in an urban area of the Maule Region, who presents skeletal muscle cystic echinococcosis. Consultation for pain, volume increase and left thigh fistula that gives out crystalline fluid. In the study with imaging techniques, multiple cystic lesions are identified in the sacral wing, iliac bone, soft tissues of the groin and left thigh. No cysts were evident in other organs. Serology Elisa IgG was positive Echinococcus granulosus. Surgical resection of soft tissue injuries. Combined antiparasitic therapy with albendazole and praziquantel was started, with good clinical response. Upon discontinuation of antiparasitic therapy at the initiative of the patient, symptoms are reinitiated.
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Equinococose/diagnóstico , Echinococcus granulosus/imunologia , Doenças Musculares/parasitologia , Coxa da Perna/parasitologia , Idoso , Animais , Doença Crônica , Ensaio de Imunoadsorção Enzimática , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças Musculares/diagnósticoRESUMO
BACKGROUND: Bites constitute a public health problem worldwide. AIM: To characterize epidemiologically bites by animals happened in the province of Los Andes (2005-2007). METHOD: Descriptive, retrospective epidemiological study. Studied variables: Bitten person (BP), accident by bite, biting animal and bite. It was not feasible to obtain more updated information by law of patient protection. RESULTS: 2,360 BP were assisted in the emergency unit of San Juan de Dios Hospital and Rio Blanco clinic. An annual average rate of 729 BP/100,000 inhabitants and 1.99 daily average was recorded. The male gender was most affected (53.5%) and the age group from 6 to 10 years old. (Rate: .521/100,000). Most frequent topographic location was the lower limb, except in children under 5 year olds in whom predominated head and neck. The biting animal according to frequency was: the dog (67.1%) spider (7.1%) and cat (3.9%). The animal property was 35.6% known and 30.7% own. The most frequent problems were: nonspecific allergy; toxic effect by spider bites and among the infections, the disease made by cats scratch stands out. Regarding the record system, the biting animal complaint was applied to 47.6% of the BP and the 92.8% of the recorded information was incomplete. CONCLUSIONS: Bites reported higher rates in the province of Los Andes than the average of the country (729 versus 188/100,000), standing out the higher magnitude in 6 to 10 year-old-children. It is noticed that the record is low and incomplete. In this province, no bite control programs or updated studies have been carried out.
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Mordeduras e Picadas/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Animais , Mordeduras e Picadas/classificação , Gatos , Criança , Pré-Escolar , Chile/epidemiologia , Cães , Serviços Médicos de Emergência , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Coelhos , Ratos , Estudos Retrospectivos , Estações do Ano , Picada de Aranha/epidemiologia , Adulto JovemRESUMO
This report summarizes the outcomes of a meeting on cystic echinococcosis (CE) in animals and humans in Chile held in Santiago, Chile, between the 21st and 22nd of January 2016. The meeting participants included representatives of the Departamento de Zoonosis, Ministerio de Salud (Zoonotic Diseases Department, Ministry of Health), representatives of the Secretarias Regionales del Ministerio de Salud (Regional Department of Health, Ministry of Health), Instituto Nacional de Desarrollo Agropecuario (National Institute for the Development of Agriculture and Livestock, INDAP), Instituto de Salud Pública (National Institute for Public Health, ISP) and the Servicio Agrícola y Ganadero (Animal Health Department, SAG), academics from various universities, veterinarians and physicians. Current and future CE control activities were discussed. It was noted that the EG95 vaccine was being implemented for the first time in pilot control programmes, with the vaccine scheduled during 2016 in two different regions in the South of Chile. In relation to use of the vaccine, the need was highlighted for acquiring good quality data, based on CE findings at slaughterhouse, previous to initiation of vaccination so as to enable correct assessment of the efficacy of the vaccine in the following years. The current world's-best-practice concerning the use of ultrasound as a diagnostic tool for the screening population in highly endemic remote and poor areas was also discussed.
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BACKGROUND: Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax (pro-apoptotic), c-myc (regulator of cell cycle) and TGF-beta1 (involved in cell differentiation) genes. METHODS: Eutopic endometrium was obtained from: 30 women with endometriosis (32.8 +/- 5 years) and 34 fertile eumenorrheic women (36 +/- 5.3 years). We analyzed apoptosis (TUNEL: DNA fragmentation); cell proliferation (immunohistochemistry (IHC) for Ki67); c-myc, bax and TGF-beta1 mRNA abundance (RT-PCR) and TGF-beta1 protein (IHC) in endometrial explants. RESULTS: Cell proliferation strongly decreased from proliferative to late secretory phases in glands, but not in stroma, in both endometria. Positive staining in glands and stroma from proliferative endometrium with endometriosis was 1.9- and 2.2-fold higher than control endometrium, respectively (p < 0.05). Abundance of c-myc mRNA was 65% higher in proliferative endometrium from endometriosis than normal tissue (p < 0.05). TGF-beta1 (mRNA and protein) augmented during mid secretory phase in normal endometrium, effect not observed in endometrium with endometriosis. In normal endometrium, the percentage of apoptotic epithelial and stromal cells increased more than 30-fold during late secretory phase. In contrast, in endometrium from endometriosis, not only this increase was not observed, besides bax mRNA decreased 63% versus normal endometrium (p < 0.05). At once, in early secretory phase, apoptotic stromal cells increased 10-fold with a concomitant augment of bax mRNA abundance (42%) in endometria from endometriosis (p < 0.05). CONCLUSION: An altered expression of c-myc, TGF-beta1 and bax was observed in eutopic endometrium from endometriosis, suggesting its participation in the regulation of cell survival in this disease. The augmented cell viability in eutopic endometrium from these patients as a consequence of a reduction in cell death by apoptosis, and also an increase in cell proliferation indicates that this condition may facilitate the invasive feature of the endometrium.
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Sobrevivência Celular/fisiologia , Endometriose/patologia , Proteínas Proto-Oncogênicas c-myc/biossíntese , Fator de Crescimento Transformador beta/biossíntese , Proteína X Associada a bcl-2/biossíntese , Adulto , Apoptose , Proliferação de Células , Fragmentação do DNA , Endométrio/citologia , Endométrio/metabolismo , Feminino , Humanos , Ciclo Menstrual/fisiologia , Fator de Crescimento Transformador beta1RESUMO
Leeches are flattened annelids or segmented worms that live in still, warm waters of the pond or in land. They feed of blood or body fluids. Medicinal leeches (Hirudo medicinalis) have been used in medicine for thousands of years to treat a wide range of ailments. Nowadays, leeches are used successfully for only a few conditions, notably in the field of reconstructive or microsurgery, to salvage tissue flaps and skin grafts whose viability is threatened by venous congestion. However, it is also important to keep it in mind as a differential diagnosis in some circumstances. This review pretends to give an actualize view of a subject that is a part of medical history.
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Sanguessugas , Aplicação de Sanguessugas/métodos , Animais , Humanos , Sanguessugas/anatomia & histologia , Sanguessugas/fisiologiaRESUMO
BACKGROUND: Toxoplasmosis, cosmopolitan parasitic zoonosis often found in humans, is transmitted mainly by food and water, and is considered a significant risk of morbidity and mortality in pregnant women, newborns and immunocompromised patients. OBJECTIVE: To identify the information about this zoonosis and its first reports in Chile. MATERIALS AND METHODS: Review of publications in Pubmed, Mesh search of systematic reviews, case studies, cross-sectional studies, systematic reviews, meta-analysis and specialty publications. In addition, other publications in parasitology journals were analyzed. CONCLUSIONS: There are reports of the presence of this disease in Chile for 60 years. During this time several differences in prevalence depending on geographic location, age and education level of the population have been detected. There is low epidemiological vigilance and lack of specific official preventive measures for this disease, despite the possible introduction of new parasite genotypes of an increased virulence and pathogenicity in the country through the importation of meat. New enigmas have arisen in relation to this disease associating it with Alzheimer, Parkinson's disease, autism, learning disabilities, among others.
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Toxoplasmose/epidemiologia , Zoonoses/epidemiologia , Animais , Chile/epidemiologia , Feminino , Humanos , Gravidez , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: The Department of Veterans Affairs (VA), the largest integrated HIV care provider in the United States (US), used the HIV Care Continuum to compare clinical care within the VA HIV population with the general US HIV population and to identify areas for improvement. METHODS: National data from the VA's HIV Clinical Case Registry were used to construct measures along the Continuum for Veterans in VA care diagnosed with HIV by June 2013 and alive by December 31, 2013. Comparisons were made to recent estimates for the same measures for the US HIV population. Additional comparisons were performed for demographic subgroups of sex, race/ethnicity, and age. RESULTS: Of 25,480 Veterans diagnosed with HIV, 77.4% were engaged in care compared with 46.3% in the US population diagnosed with HIV (P < 0.001). Seventy-three percent of Veterans diagnosed with HIV received antiretroviral therapy compared with 43% of the US population diagnosed with HIV (P < 0.001). Nearly two-thirds (65.3%) of HIV-diagnosed Veterans had suppressed HIV viral loads compared with 35.0% of the US population diagnosed with HIV (P < 0.001). CONCLUSIONS: The VA health care system performed better at every stage of the HIV Care Continuum compared with the general US estimates. Comparable high rates with some variation were noted among the demographic groups in the VA cohort. The high viral suppression rate in VA, which was almost double the estimate for the HIV-diagnosed US population, demonstrates that improved outcomes along the HIV Care Continuum can be achieved in a comprehensive integrated health care system.