Underlying and proximate drivers of biodiversity changes in Mesoamerican biosphere reserves.

Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative.

Mutation of AtPME2, a pH-Dependent Pectin Methylesterase, Affects Cell Wall Structure and Hypocotyl Elongation.

Pectin methylesterases (PMEs) modify homogalacturonan's chemistry and play a key role in regulating primary cell wall mechanical properties. Here, we report on Arabidopsis AtPME2, which we found to be highly expressed during lateral root emergence and dark-grown hypocotyl elongation. We showed that dark-grown hypocotyl elongation was reduced in knock-out mutant lines as compared to the control. The latter was related to the decreased total PME activity as well as increased stiffness of the cell wall in the apical part of the hypocotyl. To relate phenotypic analyses to the biochemical specificity of the enzyme, we produced the mature active enzyme using heterologous expression in Pichia pastoris and characterized it through the use of a generic plant PME antiserum. AtPME2 is more active at neutral compared to acidic pH, on pectins with a degree of 55-70% methylesterification. We further showed that the mode of action of AtPME2 can vary according to pH, from high processivity (at pH8) to low processivity (at pH5), and relate these observations to the differences in electrostatic potential of the protein. Our study brings insights into how the pH-dependent regulation by PME activity could affect the pectin structure and associated cell wall mechanical properties.

Effect of manipulating the vergence/accommodation and image size mismatches of the ±2D flipper test on the frequency and precision of accommodative facility.

PURPOSE: The ±2.00 D accommodative facility test presents several limitations, including the lack of objective information and inherent characteristics such as vergence/accommodative conflict, change in apparent size of the image, subjective criteria for judging blur and motor reaction time. By using free-space viewing conditions and an open-field autorefractor to monitor the refractive state, we examined the impact of manipulating these factors on the qualitative and quantitative assessment of accommodative facility. METHODS: Twenty-five healthy young adults (24.5 ± 4.5 years) took part in this study. Participants performed three accommodative facility tests (adapted flipper, 4D free-space viewing and 2.5D free-space viewing) under both monocular and binocular conditions in random order. A binocular open-field autorefractor was used to assess the accommodative response continuously, and these data were used to characterise accommodative facility quantitatively and qualitatively. RESULTS: There were statistically significant differences between the three testing methods both quantitatively (p < 0.001) and qualitatively (p = 0.02). For the same accommodative demand, a lower number of cycles was obtained for the adapted flipper condition in comparison with the 4D free-space viewing test (corrected p-value < 0.001, Cohen's d = 0.78). However, this comparison did not reach statistical significance for qualitative measures of accommodative facility (corrected p-value = 0.82, Cohen's d 0.05). CONCLUSIONS: These data provide evidence that the qualitative assessment of accommodative facility is not influenced by the inherent limitations of the ±2.00 D flipper test. The use of qualitative outcomes by incorporating an open-field autorefractor allows examiners to increase the validity of the accommodative facility test in both clinical and research settings.

Thermogravimetry coupled with mass spectrometry successfully used to quantify polyethylene and polystyrene microplastics in organic amendments.

The global consumption of plastic is growing year by year, producing small plastic pieces known as microplastics (MPs) that adversely affect ecosystems. The use of organic amendments (compost and manure) polluted with MPs affects the quality of agricultural soils, and these MPs can be incorporated into the food chain and negatively impact human health. Current European legislation only considers large plastic particles in organic amendments. There is no information regarding MP pollution. Thus, the development of a methodology to support future legislation ensuring the quality of agricultural soils and food safety is necessary. This proposed methodology is based on thermogravimetry coupled with mass spectrometry to quantify polyethylene and polystyrene (PE and PS) MPs through their mass spectrometry signal intensity of characteristic PE (m/z 41, 43 and 56) and PS (m/z 78 and 104) ions. This method has been validated with several organic amendments where the MP content ranged from 52.6 to 4365.7 mg kg-1 for PE-MPs and from 1.1 to 64.3 mg kg-1 for PS-MPs. The proposed methodology is a quick and robust analytical method to quantify MPs in organic amendments that could support new legislation.

Heating quinoa shoots results in yield loss by inhibiting fruit production and delaying maturity.

Increasing global temperatures and a growing world population create the need to develop crop varieties that provide higher yields in warmer climates. There is growing interest in expanding quinoa cultivation, because of the ability of quinoa to produce nutritious grain in poor soils, with little water and at high salinity. The main limitation to expanding quinoa cultivation, however, is the susceptibility of quinoa to temperatures above approximately 32°C. This study investigates the phenotypes, genes and mechanisms that may affect quinoa seed yield at high temperatures. Using a differential heating system where only roots or only shoots were heated, quinoa yield losses were attributed to shoot heating. Plants with heated shoots lost 60-85% yield as compared with control plants. Yield losses were the result of lower fruit production, which lowered the number of seeds produced per plant. Furthermore, plants with heated shoots had delayed maturity and greater non-reproductive shoot biomass, whereas plants with both heated roots and heated shoots produced higher yields from the panicles that had escaped the heat, compared with the control. This suggests that quinoa uses a type of avoidance strategy to survive heat. Gene expression analysis identified transcription factors differentially expressed in plants with heated shoots and low yield that had been previously associated with flower development and flower opening. Interestingly, in plants with heated shoots, flowers stayed closed during the day while the control flowers were open. Although a closed flower may protect the floral structures, this could also cause yield losses by limiting pollen dispersal, which is necessary to produce fruit in the mostly female flowers of quinoa.

Clinically significant prostate cancer detection and segmentation in low-risk patients using a convolutional neural network on multi-parametric MRI.

OBJECTIVES: To develop an automatic method for identification and segmentation of clinically significant prostate cancer in low-risk patients and to evaluate the performance in a routine clinical setting. METHODS: A consecutive cohort (n = 292) from a prospective database of low-risk patients eligible for the active surveillance was selected. A 3-T multi-parametric MRI at 3 months after inclusion was performed. Histopathology from biopsies was used as reference standard. MRI positivity was defined as PI-RADS score ≥ 3, histopathology positivity was defined as ISUP grade ≥ 2. The selected cohort contained four patient groups: (1) MRI-positive targeted biopsy-positive (n = 116), (2) MRI-negative systematic biopsy-negative (n = 55), (3) MRI-positive targeted biopsy-negative (n = 113), (4) MRI-negative systematic biopsy-positive (n = 8). Group 1 was further divided into three sets and a 3D convolutional neural network was trained using different combinations of these sets. Two MRI sequences (T2w, b = 800 DWI) and the ADC map were used as separate input channels for the model. After training, the model was evaluated on the remaining group 1 patients together with the patients of groups 2 and 3 to identify and segment clinically significant prostate cancer. RESULTS: The average sensitivity achieved was 82-92% at an average specificity of 43-76% with an area under the curve (AUC) of 0.65 to 0.89 for different lesion volumes ranging from > 0.03 to > 0.5 cc. CONCLUSIONS: The proposed deep learning computer-aided method yields promising results in identification and segmentation of clinically significant prostate cancer and in confirming low-risk cancer (ISUP grade ≤ 1) in patients on active surveillance. KEY POINTS: • Clinically significant prostate cancer identification and segmentation on multi-parametric MRI is feasible in low-risk patients using a deep neural network. • The deep neural network for significant prostate cancer localization performs better for lesions with larger volumes sizes (> 0.5 cc) as compared to small lesions (> 0.03 cc). • For the evaluation of automatic prostate cancer segmentation methods in the active surveillance cohort, the large discordance group (MRI positive, targeted biopsy negative) should be included.

Stacking three late blight resistance genes from wild species directly into African highland potato varieties confers complete field resistance to local blight races.

Considered responsible for one million deaths in Ireland and widespread famine in the European continent during the 1840s, late blight, caused by Phytophthora infestans, remains the most devastating disease of potato (Solanum tuberosum L.) with about 15%-30% annual yield loss in sub-Saharan Africa, affecting mainly smallholder farmers. We show here that the transfer of three resistance (R) genes from wild relatives [RB, Rpi-blb2 from Solanum bulbocastanum and Rpi-vnt1.1 from S. venturii] into potato provided complete resistance in the field over several seasons. We observed that the stacking of the three R genes produced a high frequency of transgenic events with resistance to late blight. In the field, 13 resistant transgenic events with the 3R-gene stack from the potato varieties 'Desiree' and 'Victoria' grew normally without showing pathogen damage and without any fungicide spray, whereas their non-transgenic equivalent varieties were rapidly killed. Characteristics of the local pathogen population suggest that the resistance to late blight may be long-lasting because it has low diversity, and essentially consists of the single lineage, 2_A1, which expresses the cognate avirulence effector genes. Yields of two transgenic events from 'Desiree' and 'Victoria' grown without fungicide to reflect small-scale farm holders were estimated to be 29 and 45 t/ha respectively. This represents a three to four-fold increase over the national average. Thus, these late blight resistant potato varieties, which are the farmers' preferred varieties, could be rapidly adopted and bring significant income to smallholder farmers in sub-Saharan Africa.

Risk factors for adolescent pregnancy in Bogotá, Colombia, 2010: a case-control study.

OBJECTIVE: To identify risk factors for adolescent pregnancy among female students in Bogotá, Colombia. METHODS: This was a retrospective study of cases and controls matched by age, identified by means of a survey on the sexual behavior of adolescent students in Bogotá (Encuesta sobre el Comportamiento Sexual de los Adolescentes Escolarizados en Bogotá) conducted in the first semester of 2010. All 272 cases and 544 randomly-selected controls were taken from 39 044 total records. Variables considered were sociodemographics, household structure, and family environment; sexual relationships and pregnancy; and knowledge of sexual and reproductive health. Matching and conditional logistic regression were used to adjust for possible confounding factors. RESULTS: The factors associated with increased risk of adolescent pregnancy based on multivariate analyses were: attending public school (odds ratio [OR]=2.25; 95% confidence interval [95% CI]: 1.45-3.51); history of siblings with adolescent pregnancy (OR =1.98; 95% CI: 1.55-2.76); early first sexual intercourse (12 years of age or less) (OR =2.34; 95% CI: 1.01-5.40); having a self-reported low- or average-level of contraceptive knowledge (OR =3.92; 95% CI: 1.96-7.83); previous pregnancy (OR =14.09; 95% CI: 8.74- 22.70); and not living with both parents (OR 3.58; 95% CI: 2.10-6.16). CONCLUSIONS: Factors related to individual, family, and social environments that influence the incidence of adolescent pregnancy must be considered and addressed when designing interventions. The existing sex education curriculum is an important component in preventing adolescent pregnancy, however, parent/caregiver participation is required for success.

Chronic disease prevalence in a population with structural hemoglobin disorders undergoing diabetes diagnosis: A bayesian approach.

Background: Structural disorders of hemoglobin are a group of rare and fatal genetic diseases that disrupt the transport and exchange of oxygen in the blood, causing tissue damage and ultimately leading to chronic conditions. The hemoglobin (Hb) S variant predominantly impacts individuals of Afro-descendant heritage. A significant concentration of the Afro-descendant population in Colombia, notably 12.5 %, is found in the city of Cali. Previous research has identified this city's structural hemoglobin disorders prevalence rate of 3.78 %. The aim of this study was to determine the prevalence of HbC, HbS, HbF, and HbA2 variants within a population who underwent HbA1c testing, as well as the prevalence of chronic diseases among patients with these hemoglobin alterations, at a high-complexity hospital in the city of Cali from 2015 to 2019. Methods: A descriptive observational study was conducted, involving a study population that comprised patients with both suspected and monitored diagnoses of diabetes. The cohort was selected from a high-complexity hospital in Cali. A total of 15,608 patients were included in the analysis, all of whom underwent HbA1C measurement through capillary electrophoresis, which also offers an indirect diagnosis of certain structural disorders of hemoglobin. Bayesian methods were employed for frequency analysis. Results: Among the 15,608 patients assessed, 63.6 % (n = 9920) were women. The overall prevalence of structural hemoglobin disorders was 1.98 % (n = 287, 95 % CI = 1.77 %-2.21 %). The co-occurrence of diabetes and kidney disease emerged as the most prevalent combination of pathologies observed in individuals with HbC, for both men and women across various age groups: 18-42 (58.3 % and 50.0 % respectively), 43-55 (50.0 % for both), 56-65 (50.0 % and 37.5 % respectively), and >65 years (66.7 % and 57.1 % respectively). Conclusions: The observed prevalence of the studied variants exceeded 1 %, a threshold underscored by the World Health Organization (WHO) as epidemiologically significant. Among HbC and HbS-positive patients, the elevated prevalence of diabetes and kidney disease is a guiding factor in developing proactive prevention strategies.

Investigating silent strokes in hypertensives: a magnetic resonance imaging study (ISSYS): rationale and protocol design.

BACKGROUND: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline.Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined.ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational cross-sectional and longitudinal study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline. METHODS/DESIGN: Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia.On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed.Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors. DISCUSSION: Improving the knowledge on the frequency and determinants of these lesions in our setting might help in the future to optimize treatments or establish new preventive strategies to minimize clinical and socioeconomic consequences of stroke and cognitive decline.

Intrahepatic cholestasis due to Treponema pallidum in an immunocompetent patient / Colestasis intrahepática por Treponema pallidum en paciente inmunocompetente

Hepatitis due to Treponema pallidum is a rare entity and its diagnosis represents a clinical challenge. Treponema pallidum should be considered as a presumptive etiology in all patients with acute liver disease, when other frequent causes have been ruled out. We present the case of a young, immunocompetent patient with elevated values in his liver tests, a cholestatic pattern, and maculopapular lesions on his palms and soles. Given his clinical picture, diagnostic tests, and response to the antimicrobial therapy, a diagnosis of cholestasis due to secondary syphilis has been established. It is important to include secondary syphilis within the possible causes of acute liver disease.

La hepatitis por Treponema pallidum es una entidad poco frecuente y su diagnóstico representa un reto clínico. Treponema pallidum debe considerarse como etiología presuntiva en todo paciente con enfermedad hepática aguda, en el cual se hayan descartado otras causas más frecuentes. Se presenta el caso de un paciente joven,  inmunocompetente, quien presentó elevación de los valores de las pruebas hepáticas con patrón colestásico y lesiones maculopapulares en palmas y plantas. Dado su cuadro clínico, las pruebas diagnósticas y la respuesta a la terapia antimicrobiana instaurada, se estableció el diagnóstico de colestasis por una sífilis secundario sifilítiao. Es importante incluir la sífilis secundaria entre las posibles causas de enfermedad hepática aguda.

Experience of the Hybrid technique for breast cancer planning in an oncology care center in Lima-Peru.

OBJECTIVE: To investigate, describe and evaluate the dosimetric parameters of the hybrid technique as a combination of the 3D Irregular Surface Compensator (3D-ISC) technique and modulated volumetric arc therapy (VMAT) for breast cancer planning. METHODS: The study involved planning a patient with left breast cancer. Planning was carried out with 3D-ISC, VMAT and Hybrid techniques. The 3 techniques were compared with respect to the target volume (PTV), coverage, gradient and protection of organs at risk (OARs). The Eclipse version 13.6 planning system was used and the prescription of the dose obeyed the hypofractionated scheme of 40.05Gy in 15 sessions (267 cGy per fraction) followed by a 13.35Gy boost in 5 sessions. RESULTS: The tangential field technique was the one with the lowest dose values delivered to healthy organs. However, with respect to the gradient, the VMAT technique was better. The Hybrid technique was the balance between the 3D-ISC and VMAT technique because after the evaluation of dosimetric parameters for both the OARs and the PTV coverage, values were found within the limits allowed according to the RTOG. CONCLUSION: The hybrid 3D-ISC and VMAT technique can be considered as a viable option for breast planning, achieving better control in OARs without losing priority over PTV coverage in addition to obtaining a good plan quality.

A protocol for Chenopodium quinoa pollen germination.

BACKGROUND: Quinoa is an increasingly popular seed crop frequently studied for its tolerance to various abiotic stresses as well as its susceptibility to heat. Estimations of quinoa pollen viability through staining methods have resulted in conflicting results. A more effective alternative to stains is to estimate pollen viability through in vitro germination. Here we report a method for in vitro quinoa pollen germination that could be used to understand the impact of various stresses on quinoa fertility and therefore seed yield or to identify male-sterile lines for breeding. RESULTS: A semi-automated method to count germinating pollen was developed in PlantCV, which can be widely used by the community. Pollen collected on day 4 after first anthesis at zeitgeber time 5 was optimum for pollen germination with an average germination of 68% for accession QQ74 (PI 614886). The optimal length of pollen incubation was found to be 48 h, because it maximizes germination rates while minimizing contamination. The pollen germination medium's pH, boric acid, and sucrose concentrations were optimized. The highest germination rates were obtained with 16% sucrose, 0.03% boric acid, 0.007% calcium nitrate, and pH 5.5. This medium was tested on quinoa accessions QQ74, and cherry vanilla with 68%, and 64% germination efficiencies, respectively. CONCLUSIONS: We provide an in vitro pollen germination method for quinoa with average germination rates of 64 and 68% on the two accessions tested. This method is a valuable tool to estimate pollen viability in quinoa, and to test how stress affects quinoa fertility. We also developed an image analysis tool to semi-automate the process of counting germinating pollen. Quinoa produces many new flowers during most of its panicle development period, leading to significant variation in pollen maturity and viability between different flowers of the same panicle. Therefore, collecting pollen at 4 days after first anthesis is very important to collect more uniformly developed pollen and to obtain high germination rates.

Heat stress changes mineral nutrient concentrations in Chenopodium quinoa seed.

Quinoa is a popular seed crop, often consumed for its high nutritional quality. We studied how heat stress in the roots or the shoots of quinoa plants affected the concentrations of 20 elements (aluminum, arsenic, boron, calcium, cadmium, cobalt, copper, iron, potassium, magnesium, manganese, molybdenum, sodium, nickel, phosphorous, rubidium, sulfur, selenium, strontium, and zinc) in quinoa seed. Elemental concentrations in quinoa seed were significantly changed after an 11-day heat treatment during anthesis. The type of panicle (main, secondary, and tertiary) sampled and the type of heat treatment (root only, shoot only, or whole plants) significantly affected elemental profiles in quinoa seed. Plants were also divided into five sections from top to bottom to assess the effect of panicle position on seed elemental profiles. Plant section had an effect on the concentrations of arsenic, iron, and sodium under control conditions and on copper with heat treatment. Overall, the time of panicle development in relation to the time of heat exposure had the largest effect on seed elemental concentrations. Interestingly, the quinoa plants were exposed to heat only during anthesis of the main panicle, but the elemental concentrations of seeds produced after heat treatment ended were still significantly changed, indicating that heat stress has long-lasting effects on quinoa plants. These findings demonstrate how the nutritional quality of quinoa seeds can be changed significantly even by relatively short heat spells.

Is Dairy Effluent an Alternative for Maize Crop Fertigation in Semiarid Regions? An Approach to Agronomic and Environmental Effects.

The reuse of effluents from intensive dairy farms combined with localized irrigation techniques (fertigation) has become a promising alternative to increase crop productivity while reducing the environmental impact of waste accumulation and industrial fertilizers production. Currently, the reuse of dairy effluents through fertigation by subsurface drip irrigation (SDI) systems is of vital importance for arid regions but it has been poorly studied. The present study aimed to assess the greenhouse gas (GHG) emissions, soil properties, and crop yield of a maize crop fertigated with either treated dairy effluent or dissolved granulated urea applied through an SDI system at a normalized N application rate of 200 kg N ha-1. Fertilizer application was divided into six fertigation events. GHG fluxes were measured during fertigation (62-day) using static chambers. Soil properties were measured previous to fertilizer applications and at the harvest coinciding with crop yield estimation. A slight increase in soil organic matter was observed in both treatments for the 20-60 cm soil depth. Both treatments also showed similar maize yields, but the dairy effluent increased net GHG emissions more than urea during the fertigation period. Nevertheless, the net GHG emissions from the dairy effluent were lower than the theoretical CO2eq emission that would have been emitted during urea manufacturing or the longer storage of the effluent if it had not been used, showing the need for life-cycle assessments. Local-specific emission factors for N2O were determined (0.07%), which were substantially lower than the default value (0.5%) of IPCC 2019. Thus, the subsurface drip irrigation systems can lead to low GHG emissions, although further studies are needed.

Obstructive sleep apnoea and 24-h blood pressure in patients with resistant hypertension.

Obstructive sleep apnoea (OSA) is common in patients with resistant hypertension, but understanding of the pathogenic mechanisms linking both conditions is limited. This study assessed the prevalence of OSA and the relationships between OSA and 24-h blood pressure (BP) in 62 consecutive patients with resistant hypertension, defined as clinic BP values ≥ 140/90 despite the prescription of at least three drugs at adequate doses, including a diuretic. In order to exclude a 'white coat effect', only patients with ambulatory 24-h BP values ≥ 125/80 were recruited. Patients underwent polysomnography, 24-h ambulatory BP monitoring and completed the Epworth sleepiness scale (ESS). OSA was defined as an apnoea-hypopnoea index (AHI) ≥ 5 and excessive daytime sleepiness (EDS) by an ESS ≥ 10. A multiple linear regression analysis was used to assess the association of anthropometric data, OSA severity measures and ESS with 24-h systolic and diastolic BP. Mean 24-h BP values were 139.14/80.98 mmHg. Ninety per cent of patients had an AHI ≥ 5 and 70% had an AHI ≥ 30. Only the ESS was associated with 24-h diastolic BP [slope 0.775, 95% confidence interval (CI) 0.120-1.390, P < 0.02); age was associated negatively with 24-h diastolic BP (slope -0.64, 95% CI -0.874 to -0.411, P < 0.001). Compared with those without EDS, patients with EDS showed a significantly higher frequency of diastolic non-dipping pattern (69.2% versus 34.7%, P < 0.032). Our results demonstrate a high prevalence of severe OSA in patients with resistant hypertension and suggest that EDS could be a marker of a pathogenetic mechanism linking OSA and hypertension.

Development and Performance of Dengue Diagnostic Clinical Algorithms in Colombia.

Diagnosing dengue in endemic areas remains problematic because of the low specificity of the symptoms and lack of accurate diagnostic tests. This study aimed to develop and prospectively validate, under routine care, dengue diagnostic clinical algorithms. The study was carried out in two phases. First, diagnostic algorithms were developed using a database of 1,130 dengue and 918 non-dengue patients, expert opinion, and literature review. Algorithms with > 70% sensitivity were prospectively validated in a single-group quasi-experimental trial with an adaptive Bayesian design. In the first phase, the algorithms that were developed with the continuous Bayes formula and included leukocytes and platelet counts, in addition to selected signs and symptoms, showed the highest sensitivities (> 80%). In the second phase, the algorithms were applied on admission to 1,039 consecutive febrile subjects in three endemic areas in Colombia of whom 25 were laboratory-confirmed dengue, 307 non-dengue, 514 probable dengue, and 193 undetermined. Including parameters of the hemogram consistently improved specificity without affecting sensitivity. In the final analysis, considering only confirmed dengue and non-dengue cases, an algorithm with a sensitivity and specificity of 65.4% (95% credibility interval 50-83) and 40.1% (34.7-45.7) was identified. All tested algorithms had likelihood ratios close to 1, and hence, they are not useful to confirm or rule out dengue in endemic areas. The findings support the use of hemograms to aid dengue diagnosis and highlight the challenges of clinical diagnosis of dengue.

Development of clinical algorithms for the diagnosis of dengue in Colombia / Desarrollo de algoritmos clínicos para el diagnóstico del dengue en Colombia

Introduction: Due to the increase in dengue incidence and mortality, its diagnosis is relevant for endemic countries. Clinical classifications and laboratory tests have a variable performance in clinical practice with a sensitivity level between 45% and 98%, and a specificity level between 4% and 98% partly due to the variety of contexts where they are applied. Objective: To develop clinical algorithms for the diagnosis of dengue in the Colombian context. Materials and methods: A cross-sectional study was conducted based on secondary sources. We constructed clinical diagnostic algorithms of dengue based on Bayesian methods combining symptoms, signs, and blood count parameters, and then we compared them in terms of diagnostic accuracy with gold standard tests. In addition, an external validation of the algorithm with greater accuracy and sensibility was performed comparing it with the WHO-1997 and the WHO-2009 clinical classifications, the Colombian guide for 2010, and the diagnostic scale recommended by the Ministerio de Salud y Protección Social of Colombia for 2013. Results: Four algorithms were generated, two for signs and symptoms, and two that included leukocytes (≤4,500/mm3) and/or platelets (≤160,000/mm3) counts. The most accurate algorithm included blood count parameters with a sensitivity of 76.5% (95%CI: 71.9-80.5) and a specificity of 46.0% (95%CI: 37.6-54.7). In the external validation we found a sensitivity of 11.1% (95%CI: 4.9-20.7) and a specificity of 91.9% (95%CI: 87.5-93.9). The scale of the Ministerio de Salud had a sensitivity of 76.4% (95%CI: 64.9-85.6) and a specificity of 38.0% (95%CI: 32.8-43.4). Conclusion: The inclusion of blood count parameters improved the sensitivity of diagnostics algorithms based on signs and symptoms. Clinical diagnosis of dengue remains a challenge for health research.

Introducción. Dado el aumento de la incidencia y la mortalidad por dengue, su diagnóstico es relevante para los países endémicos. Las clasificaciones clínicas y las pruebas de laboratorio existentes tienen un desempeño variable en la práctica clínica, pues su sensibilidad fluctúa entre 45 y 98 %, y su especificidad, entre 4 y 98 %, lo cual se debe, en parte, a la diversidad de contextos en los que se utilizan. Objetivo. Desarrollar algoritmos clínicos para el diagnóstico del dengue en el contexto colombiano. Materiales y métodos. Se hizo un estudio transversal a partir de fuentes secundarias. Se construyeron algoritmos clínicos de diagnóstico del dengue con base en métodos bayesianos que combinaron síntomas, signos y parámetros del hemograma, y se comparó su exactitud diagnóstica con la de las pruebas de referencia. Se hizo una validación externa del algoritmo de mayor exactitud y sensibilidad, comparándolo con la clasificación clínica de la Organización Mundial de la Salud de 1997 y la del 2009, con la guía colombiana del 2010 y con la escala diagnóstica propuesta por el Ministerio de Salud y Protección Social de Colombia en el 2013. Resultados. Se generaron cuatro algoritmos, dos de signos y síntomas y dos que incluyeron el conteo de leucocitos (≤4.500/mm3) o de plaquetas (≤60.000/mm3). El algoritmo de mayor exactitud incluyó los parámetros del hemograma, con una sensibilidad de 76,5 % (IC95% 71,9-80,5) y una especificidad de 46,0 % (IC95% 37,6-54,7). En la validación externa, la sensibilidad fue de 11,1 % (IC95% 4,9-20,7) y la especificidad fue de 91,9 % (IC95% 87,5-93,9). La escala del Ministerio tuvo una sensibilidad de 76,4 % (IC95% 64,9-85,6) y una especificidad de 38,0 % (IC95% 32,8-43,4). Conclusión. La inclusión de los parámetros del hemograma mejoró la sensibilidad de los algoritmos de diagnóstico basados en los signos y los síntomas. Sin embargo, el diagnóstico clínico del dengue sigue siendo un reto para la investigación en salud.

Blood pressure in the initial phase of acute ischaemic stroke: evolution and its role as an independent prognosis factor at discharge and after 3 months of follow-up.

BACKGROUND: A prospective observational study was aimed at assessing the role of blood pressure (BP) during the first 24 h from stroke onset on the outcome of acute ischaemic stroke. METHODS: Subjects admitted within the first 3 h from stroke onset were included. Stroke severity was evaluated with the Canadian Stroke Scale (CSS). Functional recovery was defined as a modified Rankin Scale score < or =2. RESULTS: One hundred subjects were included. In a logistic regression model, the independent predictors of poor functional recovery at discharge were: age (OR = 1.12; 95% CI 1.04-1.21; p = 0.0033), non-lacunar stroke subtype (OR = 4.31; 95% CI 1.07-17.31; p = 0.0395), diabetes mellitus (OR = 8.38; 95% CI 1.67-41.95; p = 0.0097), a CSS score at admission < or =8 (OR = 28.64; 95% CI 5.59-146.68; p<0.0001), an average systolic BP during the first 6 h > or =180 mmHg (OR = 13.34; 95% CI 1.34-133.10; p = 0.0272) and a lower diastolic BP average from 6 to 24 h (OR for 5 mmHg increase: 0.57; CI 95% 0.36-0.88; p = 0.0115). Similar results were observed after 3 months of follow-up. CONCLUSION: In ischaemic stroke patients, systolic BP over 180 mmHg in the first 6 h and a decrease of diastolic BP during the 6-24 h from stroke onset were independent predictors of a poor functional recovery.

De novo nephrotic syndrome following pegylated interferon alfa 2b/ribavirin therapy for chronic hepatitis C infection.

This paper describes the case of a patient with HCV, without previous evidence of nephropathy, who following two well-tolerated cycles of treatment with interferon alone developed nephrotic syndrome after a third attempt with ribavirin associated with peginterferon alfa 2b. The patient exhibited a total remission when the antiviral treatment was discontinued.