Evaluation of highly sensitive diagnostic tools for the detection of P. falciparum in pregnant women attending antenatal care visits in Colombia.

BACKGROUND: In low transmission settings early diagnosis is the main strategy to reduce adverse outcomes of malaria in pregnancy; however, microscopy and rapid diagnostic tests (RDTs) are inadequate for detecting low-density infections. We studied the performance of the highly sensitive-RDT (hsRDT) and the loop mediated isothermal DNA amplification (LAMP) for the detection of P. falciparum in pregnant women. METHODS: A cross-sectional study was conducted in two malaria-endemic municipalities in Colombia. We screened pregnant women in the context of an antenatal care program in health facilities and evaluated five tests (microscopy, conventional RDT, hsRDT, LAMP and nested polymerase chain reaction-PCR) for the detection of P. falciparum in peripheral blood, using a quantitative reverse transcription PCR (qRT-PCR) as the reference standard. Diagnostic performance of hsRDT and LAMP were compared with routine testing. RESULTS: The prevalence of P. falciparum was 4.5% by qRT-PCR, half of those infections were subpatent. The sensitivity of the hsRDT (64.1%) was slightly better compared to microscopy and cRDT (59 and 53.8% respectively). LAMP had the highest sensitivity (89.7%) for detecting P. falciparum and the ability to detect very low-density infections (minimum parasite density detected 0.08 p/µL). CONCLUSIONS: There is an underestimation of Plasmodium spp. infections by tests routinely used in pregnant women attending antenatal care visits. LAMP methodology can be successfully implemented at local hospitals in malaria-endemic areas. The relevance of detecting and treating this sub-patent P. falciparum infections in pregnant women should be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172221 , Date of registration: May 29, 2017.

Bariatric Surgery Waiting Lists in Spain.

Bariatric surgery is one of the most common general surgery procedures in countries that, like Spain, have public healthcare systems, but is also one of the procedures for which patients have to wait the longest. The Spanish Society of Obesity Surgery (SECO) conducted a survey to estimate the situation of bariatric surgery waiting lists in Spain's public hospitals and to gather information on a number of related aspects. METHODS: An online survey was sent to the members of the SECO. The survey received 137 visits, all via the click-through link provided, from 52 health centers (47 public and 5 private). The data collected were included in a database and later analyzed using the SPSS18.0 statistical software package. RESULTS: A total of 4724 patients were on bariatric surgery waiting lists (BWLs), at an average of 100 per public hospital. Sixty-eight percent had been waiting for more than 6 months. The mean delay per patient was 397 days, and the longest wait was 1661 days. A further 46.2% of respondents were able to recall cases of patients who in the past 5 years had suffered cardiovascular events with sequelae while awaiting surgery, and 21.2% recalled at least one fatal cardiovascular event in that time. CONCLUSION: Our data revealed an unacceptably long wait for obesity surgery. Notwithstanding the limitations and potential biases of our research, the long wait for surgery in our context inevitably has serious consequences for a potentially significant number of patients.

BNNT/Fe3O4 System as an Efficient Tool for Magnetohyperthermia Therapy.

Nanostructured materials have been widely studied aiming to biomedical applications, primarily for the purpose of carrying drugs or molecules of interest in a selected tissue or organ. In this context, boron nitride nanotubes (BNNTs), when functionalized with specific moieties, could be useful as nanovectors for delivery of proteins, drugs, and also RNAi molecules, due to their capacity to be uptaked by cells. The introduction of magnetic nanoparticles allows the use of such system as a hyperthermia agent. Thus, once it has been targeted to tumor areas, it could kill cancer cells by magnetohyperthermia therapy. In order to study this effect, magnetite nanoparticles were incorporated into hydroxilated BNNT. The system was characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and vibrating sample magnetometry (VSM). The results obtained show that magnetite nanoparticles are linked to the nanotubes. Magnetic measurements show that coercivity and magnetization were not disturbed after incorporation to the BNNT. Based on this, a new methodology for in vitro magnetohyperthermia experiments was developed, aiming to treat each cell group individually preserving its sterility. The biological assays of the system demonstrate its good cell viability and the great potential of this nanomaterial as a magnetohyperthermia agent for cancer treatment.

Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.

Implication of different domains of the Leishmania major metacaspase in cell death and autophagy.

Metacaspases (MCAs) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine-cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. The role of MCAs is subject to debate: roles in cell cycle control, in cell death or even in cell survival have been suggested. In this study, using a Leishmania major MCA-deficient strain, we showed that L. major MCA (LmjMCA) not only had a role similar to caspases in cell death but also in autophagy and this through different domains. Upon cell death induction by miltefosine or H2O2, LmjMCA is processed, releasing the catalytic domain, which activated substrates via its catalytic dyad His/Cys and a proline-rich C-terminal domain. The C-terminal domain interacted with proteins, notably proteins involved in stress regulation, such as the MAP kinase LmaMPK7 or programmed cell death like the calpain-like cysteine peptidase. We also showed a new role of LmjMCA in autophagy, acting on or upstream of ATG8, involving Lmjmca gene overexpression and interaction of the C-terminal domain of LmjMCA with itself and other proteins. These results allowed us to propose two models, showing the role of LmjMCA in the cell death and also in the autophagy pathway, implicating different protein domains.

Significance of linkage disequilibrium heterogeneous patterns in the 21q22.3 region for mapping 21 trisomy individuals.

Recombination patterns can be indirectly inferred by means of linkage disequilibrium (LD) estimates, since LD is negatively correlated with genetic distance. However, LD does not necessarily have absolute correspondence with genetic distance. We estimated LD at 5 loci located in the 21q22.3 region. These STRs (D21S1440, D21S168, D21S1260, D21S1446, and D21S1411) covered 8.81 Mb of the 21q22.3 region. They were genotyped by conventional PCR. Similar size samples previously validated by sequencing were used as a genotyping control. Three hundred and sixty-nine individuals (62 families) living in Guadalajara, Mexico, were included. As an inclusion criterion, each family had a positive paternity test by autosomal markers for the CODIS core loci. Two hundred and thirty phase known haplotypes were identified by familial segregation. Only those haplotypes whose frequency was higher than 4% were taken into account for LD estimation, expressed as Lewontin's D' coefficient and Bonferroni's correction P values. For all 5 loci, the genetic distributions were in agreement with Hardy-Weinberg expectations. Heterozygosity and haplotype diversity were ≥ 0.69 and 99.58%, respectively. D21S1440-D21S168 (4.51 cM) and D21S1446-D21S1411 (4.58 cM) marker haplotype frequencies were significantly different from those expected by random distribution. The remaining haplotypes, including those with minimal inter-distance (D21S1260-D21S1446, 1.44 Mb), did not show LD. The 5 STRs at the 21q22.3 region in this Mexican population showed a non-homogeneous LD pattern, which demonstrates that recombination or linkage should not be assumed solely on the basis of genetic distance.

The submarine volcano eruption at the island of El Hierro: physical-chemical perturbation and biological response.

On October 10 2011 an underwater eruption gave rise to a novel shallow submarine volcano south of the island of El Hierro, Canary Islands, Spain. During the eruption large quantities of mantle-derived gases, solutes and heat were released into the surrounding waters. In order to monitor the impact of the eruption on the marine ecosystem, periodic multidisciplinary cruises were carried out. Here, we present an initial report of the extreme physical-chemical perturbations caused by this event, comprising thermal changes, water acidification, deoxygenation and metal-enrichment, which resulted in significant alterations to the activity and composition of local plankton communities. Our findings highlight the potential role of this eruptive process as a natural ecosystem-scale experiment for the study of extreme effects of global change stressors on marine environments.

Carcinoma de pulmón: cambios en epidemiología y supervivencia / Lung cancer: changes in epidemiology and survival

Antecedentes y objetivo. En las últimas décadas se han descrito variaciones en la epidemiología del carcinoma de pulmón. Hemos analizado si se han producido cambios en la epidemiología y la supervivencia del carcinoma de pulmón. Pacientes y métodos. Se incluyeron todos los casos con el diagnóstico de carcinoma de pulmón, con confirmación citohistológica entre mayo de 1997 y diciembre de 2008. Para comparar las variables analizadas se dividió el período de estudio en tres cohortes comprendidas respectivamente entre los años 1997-2000, 2001-2004 y 2005-2008. Resultados. Se incluyeron 905 pacientes, 776 varones (85,7%), con una edad media (± DE) de 64,4±11,6 años. El número de mujeres se incrementó desde el 11,2% en 1997-2000 hasta el 16,2% en 2005-2008. La estirpe adenocarcinoma aumentó desde el 29,3% en 1997-2000 hasta el 34,5% en 2005-2008 (p=0,02). La mediana de supervivencia se incrementó en 10 semanas: 51 semanas en 1997-2000 y 61 semanas en 2005-2008 (p=0,2). La supervivencia se asoció de forma independiente con el grado de actividad, tratamiento recibido, comorbilidad y pérdida de peso. Conclusiones. En nuestra área se ha producido un incremento del número de casos de cáncer de pulmón en las mujeres. Ha aumentado el tipo histológico de adenocarcinoma, y apreciamos un leve aumento de la supervivencia(AU)

Background and objective. In the last decades, variations have been described in the epidemiology of lung cancer. In our study, we have analyzed if changes have occurred in the epidemiology and survival of lung cancer. Patients and methods. All the cases with the diagnosis of lung cancer having cytohistological confirmation between May 1997 and December 2008 were included. To compare the variables, the study period was divided into three cohorts, respectively including the years 1997-2000, 2001-2004 and 2005-2008. Results. A total of 905 patients, 776 males (85.7%) were included with a mean age (± SD) of 64.4±11.6 years. The number of cases in females went from 11.2% in 1997-2000 to 16.2% in 2005-2008, and adenocarcinoma from 29.3% to 34.5% (P=.2). Survival was associated independently with the performance status, treatment, comorbidity and weight loss. Conclusions. In our area, there is been an increasing number of cases of lung cancer in females. The histological type of adenocarcinoma has increased and we have observed a slight increase in survival(AU)

[Lung cancer: changes in epidemiology and survival]. / Carcinoma de pulmón: cambios en epidemiología y supervivencia.

BACKGROUND AND OBJECTIVE: In the last decades, variations have been described in the epidemiology of lung cancer. In our study, we have analyzed if changes have occurred in the epidemiology and survival of lung cancer. PATIENTS AND METHODS: All the cases with the diagnosis of lung cancer having cytohistological confirmation between May 1997 and December 2008 were included. To compare the variables, the study period was divided into three cohorts, respectively including the years 1997-2000, 2001-2004 and 2005-2008. RESULTS: A total of 905 patients, 776 males (85.7%) were included with a mean age (± SD) of 64.4 ± 11.6 years. The number of cases in females went from 11.2% in 1997-2000 to 16.2% in 2005-2008, and adenocarcinoma from 29.3% to 34.5% (P=.2). Survival was associated independently with the performance status, treatment, comorbidity and weight loss. CONCLUSIONS: In our area, there is been an increasing number of cases of lung cancer in females. The histological type of adenocarcinoma has increased and we have observed a slight increase in survival.

Cathepsin B-like and cell death in the unicellular human pathogen Leishmania.

In several studies reporting cell death (CD) in lower eukaryotes and in the human protozoan parasite Leishmania, proteolytic activity was revealed using pan-caspase substrates or inhibitors such as carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK). However, most of the lower eukaryotes do not encode caspase(s) but MCA, which differs from caspase(s) in its substrate specificity and cannot be accountable for the recognition of Z-VAD-FMK. In the present study, we were interested in identifying which enzyme was capturing the Z-VAD substrate. We show that heat shock (HS) induces Leishmania CD and leads to the intracellular binding of Z-VAD-FMK. We excluded binding and inhibition of Z-VAD-FMK to Leishmania major metacaspase (LmjMCA), and identified cysteine proteinase C (LmjCPC), a cathepsin B-like (CPC) enzyme, as the Z-VAD-FMK binding enzyme. We confirmed the specific interaction of Z-VAD-FMK with CPC by showing that Z-VAD binding is absent in a Leishmania mexicana strain in which the cpc gene was deleted. We also show that parasites exposed to various stress conditions release CPC into a soluble fraction. Finally, we confirmed the role of CPC in Leishmania CD by showing that, when exposed to the oxidizing agent hydrogen peroxide (H(2)O(2)), cpc knockout parasites survived better than wild-type parasites (WT). In conclusion, this study identified CPC as the substrate of Z-VAD-FMK in Leishmania and as a potential additional executioner protease in the CD cascade of Leishmania and possibly in other lower eukaryotes.

Molecular characterization of a patient with 3p deletion syndrome and a review of the literature.

3p deletion syndrome is a rare disorder involving developmental delay, dysmorphic physical features, and growth retardation. Molecular mapping of several cases in the literature have identified a critical region on chromosome 3p26. We present a child patient with characteristic features of 3p deletion syndrome and a de novo unbalanced translocation involving chromosomes 3 and 13. Fine mapping of this rearrangement using fluorescence in situ hybridization (FISH) and array-based comparative genomic hybridization (aCGH) revealed an unbalanced abnormality including a 4.5 Mb terminal deletion of chromosome 3p, telomeric to ITPR1 on 3p26.2, which was not previously identified with routine cytogenetic analysis. In addition, these investigations confirmed and refined the boundaries of a 26.5 Mb deletion of chromosome 13. This study confirms the minimal candidate region for 3p deletion syndrome, provides further evidence implicating haploinsufficiency of CNTN4 in the disorder, and demonstrates the utility of high-resolution investigations of rare chromosomal rearrangements.

[Transbronchial needle aspiration in bronchogenic carcinoma with visible lesions: diagnostic yield and cost]. / Punción transbronquial en el carcinoma broncogénico con lesión visible: rendimiento y coste económico.

BACKGROUND: Transbronchial needle aspiration (TBNA) is a bronchoscopic technique whose usefulness in diagnosing endobronchial lesions has not yet been clearly established. OBJECTIVE: We aimed to determine whether the diagnostic yield of fiberoptic bronchoscopy could be increased, without a negative impact on diagnostic costs, if TBNA were used in combination with conventional diagnostic techniques (bronchial washings and bronchial brushings and forceps biopsy). PATIENTS AND METHODS: The cases of 130 patients diagnosed with bronchogenic carcinoma with endoscopically visible lesions were analyzed retrospectively. All had undergone conventional diagnostic procedures; TBNA was also performed if the bronchoscopist considered it was indicated. The final cost was calculated in euros for each diagnosis as the sum of the cost of the procedures needed to reach the diagnosis, including both endoscopic procedures and others (transthoracic needle aspiration, lymph node biopsy). Diagnostic yield and costs in cases diagnosed using only conventional techniques were compared to the yield and costs in cases in which both conventional techniques and TBNA were used. RESULTS: TBNA was performed in 49 patients and provided the diagnosis in 85.7%. Conventional techniques led to cytological and histological diagnosis in 80.2% of the cases, and the combination of conventional techniques and TBNA gave a diagnosis in 89.7% (P=.01). Significant differences were observed in extrinsic compression (conventional 37.5%; conventional+TBNA 100%; P=.01), submucosal infiltration (conventional 54.6%; conventional+TBNA 85%; P=.03), and exophytic mass with necrosis (conventional 80%; conventional+TBNA 100%; P=.01). The mean (SD) cost of diagnosis was euros 381.60 (euros 156.53) using conventional techniques and euros 413.25 (euros 112.91) for conventional techniques in combination with TBNA. By adding TBNA, costs decreased for diagnoses of submucosal infiltration, exophytic mass with necrosis and extrinsic compression, although the saving was significant only for extrinsic compression. CONCLUSION: The diagnostic yield of TBNA is high for endoscopically visible bronchial anomalies suggesting neoplasm, particularly when the lesion is due to extrinsic compression, submucosal infiltration, or exophytic mass with necrosis.

Punción transbronquial en el carcinoma broncogénicocon lesión visible: rendimiento y coste económico / Transbronchial needle aspiration in bronchogenic carcinoma with visible lesions: diagnostic yield and cost

FUNDAMENTO: La punción transbronquial (PTB) es una técnica broncoscópica cuya utilidad en tumores con lesión endobronquial no está claramente establecida.OBJETIVO: Con nuestro trabajo pretendemos estudiar si la combinación de la PTB con las técnicas diagnósticas convencionales (aspirado, cepillado y biopsia bronquiales) incrementa el rendimiento de la fibrobroncoscopia, sin repercutir negativamente en el coste económico (CE) del proceso diagnóstico. PACIENTES Y MÉTODOS: Se analizó de forma retrospectiva a 130 pacientes diagnosticados de carcinoma broncogénico con lesión endoscópica visible, a quienes se les practicaron las técnicas convencionales, quedando a criterio del broncoscopista responsable la realización de PTB. Se calculó el coste final por proceso, en euros, constituido por la suma del coste de los procedimientos necesarios para lograr el diagnóstico, en los que se incluían los endoscópicos y otros (punción transtorácica, punción-biopsia ganglionar). Se compararon el rendimiento y el CE entre el grupo de pacientes a los que se practicaron las técnicas convencionales (ACB) y aquellos a los que se añadió PTB (ACB + PTB). RESULTADOS: La PTB se realizó en 49 pacientes y proporcionó el diagnóstico de naturaleza en el 85,7 por ciento de los casos. Con ACB se logró la filiación citohistológica en el 80,2 por ciento de los casos, y en el 89,7 por ciento con ACB + PTB (p = 0,01); se apreciaron diferencias significativas en: compresión extrínseca (ACB: 37,5 por ciento; ACB + PTB: 100 por ciento; p = 0,01), infiltración submucosa (ACB: 54,6 por ciento; ACB + PTB: 85 por ciento; p = 0,03) y masa exofítica con necrosis (ACB: 80 por ciento; ACB + PTB: 100 por ciento; p = 0,01). El CE medio fue de 381,60 ñ 156,53 euros en ACB y 413,25 ñ 112,91 en ACB + PTB; al añadir la PTB se redujo el CE en infiltración submucosa, masa exofítica con necrosis y compresión extrínseca, aunque este ahorro sólo resultó significativo en compresión extrínseca. CONCLUSIÓN: La punción transbronquial es una técnica de elevada rentabilidad en presencia de anomalías endobronquiales indicativas de neoformación, particularmente cuando la lesión visualizada corresponde a compresión extrínseca, infiltración submucosa o masa exofítica con superficie necrótica (AU)

Coagulación intravascular diseminada como forma de presentación de adenocarcionma prostático / Disseminated intravascular coagulation as presentation of prostatic adenocarcinoma

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Carcinoma broncogénico no microcítico en estadios avanzados: influencia pronóstica de la pérdida de peso e implicaciones clínicas / Non-small cell bronchogenic carcinoma in advanced stages: prognostic value of weight loss and clinical implications

OBJETIVOS: Se diseñó un estudio en carcinoma broncogénico no microcítico en estadios avanzados, con los siguientes objetivos: a) identificar factores pronósticos recogidos en el momento del diagnóstico, y b) precisar si la pérdida de peso es un parámetro útil para seleccionar a los sujetos que obtendrían un mayor beneficio del tratamiento oncológico. PACIENTES MÉTODOS: Se incluyó a 81 pacientes diagnosticados de carcinoma broncogénico no microcítico en estadios III-b y IV y con grado de actividad menor de 2 según ECOG. Las variables a estudiar fueron: edad, sexo, antecedentes de tabaquismo, comorbilidad, datos clínicos (pérdida de peso, disnea, síndrome de vena cava superior), parámetros de laboratorio (hemoglobina, albúmina sérica, linfocitos totales, lactatodeshidrogenasa sérica, calcemia y enzimas hepáticas), tipo histológico, grado de actividad, estadificación tumoral (TNM), tratamiento recibido y supervivencia en semanas. Se analizaron dos grupos: grupo general, formado por todos los pacientes, y grupo sin pérdida de peso, constituido por los sujetos en que estaba ausente este síntoma. Para el estudio estadístico y de supervivencia se utilizaron las siguientes pruebas: t de Student, 2, Kaplan-Meier, test de rangos logarítmos y modelos de regresión de Cox. RESULTADOS: La mediana de supervivencia fue de 29 semanas (rango: 21-37). En el grupo general presentaban una relación significativa con la supervivencia los siguientes parámetros: pérdida de peso, linfocitos totales, LDH sérica, TNM y grado de actividad. De éstos, sólo mantenían implicación pronóstica en el estudio multivariado de pérdida de peso (HR: 1,48 [1,14-1,92]; p = 0,002) y la TNM (HR: 0,72 [0,54-0,96]; p = 0,02). En el grupo sin pérdida de peso en el univariado tienen relación significativa el tratamiento recibido y la TNM, conservando ambas una correlación con el pronóstico al incluirlas en modelos de regresión de Cox. CONCLUSIONES: En nuestra experiencia, en carcinoma de pulmón en estadios avanzados subsidiarios de tratamiento oncológico, la pérdida de peso es la variable con mayor poder pronóstico, por lo que podría ser conveniente considerarla de manera rutinaria, conjuntamente con el grado de actividad, para intentar identificar a los pacientes que obtendrían un mayor beneficio del tratamiento citostático (AU)

Pelagra: manifestaciones de una enfermedad... ¿no olvidada? / Pellagra: manifestations of disease...not forgotten?

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