First babies conceived with Automated Intracytoplasmic Sperm Injection.

RESEARCH QUESTION: Can an automated sperm injection robot perform Automated Intracytoplasmic Sperm Injection (ICSIA) for use in human IVF? DESIGN: The ICSIA robot automated the sperm injection procedure, including injection pipette advancement, zona pellucida and oolemma penetration with piezo pulses, and pipette removal after sperm release. The robot was first tested in mouse, hamster and rabbit oocytes, and subsequently using discarded human oocytes injected with microbeads. A small clinical pilot trial was conducted with donor oocytes to study the feasibility of the robot in a clinical setting. The ICSIA robot was controlled by engineers with no micromanipulation experience. Results were compared with those obtained with manual ICSI conducted by experienced embryologists. RESULTS: The ICSIA robot demonstrated similar results to the manual procedure in the different animal models tested as well as in the pre-clinical validations conducted in discarded human oocytes. In the clinical validation, 13 out of 14 oocytes injected with ICSIA fertilized correctly versus 16 out of 18 in the manual control; eight developed into good-quality blastocysts versus 12 in the manual control; and four were diagnosed as chromosomally normal versus 10 euploid in the manual control. Three euploid blastocysts from the ICSIA robot group have been transferred into two recipients, which resulted in two singleton pregnancies and two babies born. CONCLUSIONS: The ICSIA robot showed high proficiency in injecting animal and human oocytes when operated by inexperienced personnel. The preliminary results obtained in this first clinical pilot trial are within key performance indicators.

Resting metabolic rate in relation to incident disability and mobility decline among older adults: the modifying role of frailty.

BACKGROUND: Alterations in resting metabolic rate (RMR), the largest component of daily total energy expenditure, with aging have been shown in various studies. However, little is known about the associations between RMR and health outcomes in later life. AIMS: To analyze whether RMR is associated with incident disability and mobility decline in a 10-year longitudinal study, as well as the moderating role of frailty in these associations. METHODS: Data from 298 older adults aged 70 and over from the Frailty and Dependence in Albacete (FRADEA) study in Spain were used, including a baseline measurement in 2007-2009 and a follow-up measurement 10 years later. RMR was measured by indirect calorimetry. Outcomes were incident disability in basic activities of daily living (BADL, Barthel Index), incident disability in instrumental ADL (IADL, Lawton index), and mobility decline (Functional Ambulation Categories scores). Fried's frailty phenotype was used as an indicator of frailty. Logistic regression analyses were conducted. RESULTS: Fully adjusted and stratified analyses revealed that only in the pre-frail/frail group, a higher RMR was associated with a lower risk of incident BADL disability (OR = 0.47, 95% CI = 0.23-0.96, p = 0.037), incident IADL disability (OR = 0.39, 95% CI = 0.18-0.84, p = 0.017), and mobility decline (OR = 0.30, 95% CI = 0.14-0.64, p = 0.002). CONCLUSIONS: To our knowledge, this is the first study looking at the associations between RMR and functional health using a longitudinal research design. The results suggest that RMR could be used as an early identifier of a specific resilient group within the pre-frail and frail older population, with a lower risk of further health decline.

Psychological and Functional Impact of COVID-19 in Long-Term Care Facilities: The COVID-A Study.

OBJECTIVE: To analyze the psychological and functional sequelae of the COVID-19 pandemic among older adults living in long term care facilities (LTCFs). DESIGN: Cohort longitudinal study SETTING ANT PARTICIPANTS: A total of 215 residents ≥ 65 years without moderate-to-severe cognitive impairment, living in five LTCFs in Albacete (Spain). MEASUREMENTS: Baseline on-site data were collected between March - June 2020 and three-month follow-up between June to September 2020. Symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), and sleep disturbances were measured as psychological variables. Disability in basic activities of daily living (BADL), ambulation and frailty were assessed as functional variables. Differences were analyzed in relation to level of comorbidity and test positivity for COVID-19. RESULTS: At baseline, residents with COVID-19 presented worse functionality, higher frailty levels and malnutrition risk compared to non-COVID-19 residents. At three-month follow-up, higher rates of clinically significant depressive symptoms (57.7%), anxiety symptoms (29.3%), PTSD symptoms (19.1%) and sleep disturbances (93.0%) were found among residents regardless of COVID status. Thus, among 215 residents, 101 (47%) experienced a decline in BADL from baseline to the 3-month follow-up (median functional loss = 5 points in Barthel Index). In multivariate analyses, COVID-19 status did not explain either the functional or the ambulation loss. By contrast, residents with low comorbidity and COVID-19 presented higher PTSD symptoms (effect 2.58; 95% CI 0.93 to 4.23) and anxiety symptoms (effect 2.10; 95% CI 0.48 to 3.73) compared to the low comorbidity/non-COVID19 group. CONCLUSION: COVID-19 pandemic was associated, after three-months, with high psychological impact in older adults in LTCFs., specifically with higher post-traumatic stress and anxiety symptoms. Functional decline did not differ in relation to COVID-19 status but could be related to isolation strategies used for pandemic control.

Mechanical and electrical properties of MWCNTs - high early strength cement - mortars composite: Dispersion of CNTs and effect of chemical admixtures.

The objectives of this research were to study (1) the dispersion of MWCNTs in an aqueous system by three commercial admixtures (CAds) for concrete, and (2) the effect of CAds and MWCNTs on indirect tensile strength and electrical conductivity of MWCNTs-high early strength (HE) cement-mortar composites. To achieve the objectives, we dispersed MWCNTs in an aqueous system with (1) hydroxylated polymers-based water reducing plasticizer (HPs), a nonionic compound, (2) Naphthalene based superplasticizer (SNF), an anionic compound, and (3) calcium chloride-based accelerating agent (CC) a neutral amphoteric salt. We prepared a total of 242 samples grouped in three sets: (1) Plain mortar [PM] (water + HE cement + Sand), (2) [PM+CAd], and (3) [PM+CAd+MWCNTs]. The three CAds dispersed MWCNTs in an aqueous solution. The CC and HPs admixtures have a two-time bigger dispersing power than the SNF. They demand half of SNF's ultrasound energy for optimal dispersion. Although the SNF (anionic) based superplasticizer resulted incompatible with the HE cement, it improved the indirect tensile strength of [PM+SNF+MWCNTs] composite. In contrast, the CC (amphoteric) based accelerating agent was compatible with the HE cement; the CC adsorption on the MWCNTs surface favors an improvement in the electrical conductivity of [PM+CAd+MWCNTs] composite.

A histologic scoring system for prognosis of patients with alcoholic hepatitis.

BACKGROUND & AIMS: There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality. METHODS: We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. RESULTS: The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0-3 points), moderate (4-5 points), or high (6-9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. CONCLUSIONS: We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making.

DNA methylation pattern of gene promoters of major neurotransmitter systems in older patients with schizophrenia with severe and mild cognitive impairment.

OBJECTIVE: To analyze, in older patients with schizophrenia, the methylation status of a set of genes associated with the pathophysiology of the disorder but including anatomical, clinical, and cognitive criteria in the experimental design that, in conjunction with the epigenetic status of specific genes, allows us to derive an integrative model. METHOD: This study included 29 human brain samples from older schizophrenic patients with severe and mild cognitive impairment. We administered a comprehensive battery of neurocognitive tests to determine the size of the impairment across different cognitive domains. We focused our study on the analysis of the methylation pattern of 19 genes of major neurotransmitter systems using methylation-specific PCR and bisulfite genomic sequencing. RESULTS: Our results highlight an absence of hypermethylation and hypomethylation in older patients with schizophrenia and in healthy controls, irrespective of the degree of the cognitive deficit measured in the neuropsychological assessment (Fisher's exact test; p<0.05). CONCLUSION: mRNA or protein expression level differences in genes of major neurotransmitter systems that are known to be altered in schizophrenia must be because of regulatory mechanisms other than the DNA methylation of its promoter regions, although our results highlight the idea that the analysis of the epigenetic mechanisms involved in schizophrenia represents a new approach that has the possibility of uncovering molecular mechanisms of dysregulated gene expression in this complex disorder.

Advanced Paternal Age: A New Indicator for the Use of Microfluidic Devices for Sperm DNA Fragmentation Selection.

New social conditions and progress in ART have both contributed to the delay in parenthood in developed countries. While the effects of maternal age have been widely studied, paternal age is poorly understood, and there are no specific guides on ART techniques to treat its deleterious effects. It is known that there is an increase in sperm DNA fragmentation (SDF) in elderly men, and new sperm selection devices using microfluids have been developed. This study analyses 189 ICSI cycles with donor oocytes performed between January 2018 and February 2022. Spermatozoa were selected using an MSS device or density gradients, followed by ICSI fertilization and fresh/thawed embryo transfer. We assessed the association between the selection technique, paternal age (< or ≥45) and reproductive outcomes. Fertilization (FR), blastulation (BR), implantation (IR), live-birth (LBR) and miscarriage (MR) rates were calculated. The results showed significantly higher IR (57.7% vs. 42.5%) and LBR (42.9% vs. 30.3%) when applying MSS selection, and particularly higher BR, IR and LBR when the paternal age was equal to or over 45 years (BR: 64.4 ± 23% vs. 50.1 ± 25%, IR: 51.5% vs. 31.6% and LBR: 42.4% vs. 23.7%). We also found a negative correlation between BR and paternal age (r2 = 0.084). The findings show that MSS enhances success in assisted reproduction cycles with ICSI, especially in couples with advanced paternal age. We propose advanced paternal age as a new indicator for the application of sperm selection techniques that reduce fragmentation.

Effects of PEEP on intracranial pressure in patients with acute brain injury: An observational, prospective and multicenter study.

OBJECTIVE: To analyze the impact of positive end-expiratory pressure (PEEP) changes on intracranial pressure (ICP) dynamics in patients with acute brain injury (ABI). DESIGN: Observational, prospective and multicenter study (PEEP-PIC study). SETTING: Seventeen intensive care units in Spain. PATIENTS: Neurocritically ill patients who underwent invasive neuromonitorization from November 2017 to June 2018. INTERVENTIONS: Baseline ventilatory, hemodynamic and neuromonitoring variables were collected immediately before PEEP changes and during the following 30 min. MAIN VARIABLES OF INTEREST: PEEP and ICP changes. RESULTS: One-hundred and nine patients were included. Mean age was 52.68 (15.34) years, male 71 (65.13%). Traumatic brain injury was the cause of ABI in 54 (49.54%) patients. Length of mechanical ventilation was 16.52 (9.23) days. In-hospital mortality was 21.1%. PEEP increases (mean 6.24-9.10 cmH2O) resulted in ICP increase from 10.4 to 11.39 mmHg, P < .001, without changes in cerebral perfusion pressure (CPP) (P = .548). PEEP decreases (mean 8.96 to 6.53 cmH2O) resulted in ICP decrease from 10.5 to 9.62 mmHg (P = .052), without changes in CPP (P = .762). Significant correlations were established between the increase of ICP and the delta PEEP (R = 0.28, P < .001), delta driving pressure (R = 0.15, P = .038) and delta compliance (R = -0.14, P = .052). ICP increment was higher in patients with lower baseline ICP. CONCLUSIONS: PEEP changes were not associated with clinically relevant modifications in ICP values in ABI patients. The magnitude of the change in ICP after PEEP increase was correlated with the delta of PEEP, the delta driving pressure and the delta compliance.

A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C.

BACKGROUND & AIMS: Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS: 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS: Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS: MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.

Best practices in survivor engagement in IRCT member centres.

INTRODUCTION: While the literature encourages engaging torture survivors in the direction and provision of services, little is known about how best to do this. METHOD: We surveyed 82 member centres of the International Rehabilitation Council for TortureVictims (IRCT), a worldwide network of anti-torture organisations, and interviewed fourteen staff members and executive directors about current practices, best practices, and the advantages and disadvantages of engaging survivors. RESULTS: While few agencies involve survivors extensively, those that did found survivor engagement helped agencies engage in better planning, service provision, and advocacy, while at the same time being healing and empowering for survivors. Agency staff described strategies to minimize retraumatization, particularly in not encouraging survivors to share the story of their trauma, but to engage in other ways. Agency staff suggested a number of ways to engage survivors in program direction, service provision, and advocacy, which included having survivors serve on the board of directors, hiring survivors as staff, involving survivors in advocacy, advising staff and volunteers on how better to provide services, and working as community outreach workers and mediators. CONCLUSION: IRCT member centres can engage survivors in programming without retraumatizing them, and there are many advantages to doing so.

Novel Time-Lapse Parameters Correlate with Embryo Ploidy and Suggest an Improvement in Non-Invasive Embryo Selection.

Selecting the best embryo for transfer is key to success in assisted reproduction. The use of algorithms or artificial intelligence can already predict blastulation or implantation with good results. However, ploidy predictions still rely on invasive techniques. Embryologists are still essential, and improving their evaluation tools can enhance clinical outcomes. This study analyzed 374 blastocysts from preimplantation genetic testing cycles. Embryos were cultured in time-lapse incubators and tested for aneuploidies; images were then studied for morphokinetic parameters. We present a new parameter, "st2, start of t2", detected at the beginning of the first cell cleavage, as strongly implicated in ploidy status. We describe specific cytoplasmic movement patterns associated with ploidy status. Aneuploid embryos also present slower developmental rates (t3, t5, tSB, tB, cc3, and t5-t2). Our analysis demonstrates a positive correlation among them for euploid embryos, while aneuploids present non-sequential behaviors. A logistic regression study confirmed the implications of the described parameters, showing a ROC value of 0.69 for ploidy prediction (95% confidence interval (CI), 0.62 to 0.76). Our results show that optimizing the relevant indicators to select the most suitable blastocyst, such as by including st2, could reduce the time until the pregnancy of a euploid baby while avoiding invasive and expensive methods.

Improving the remote estimation of soil organic carbon in complex ecosystems with Sentinel-2 and GIS using Gaussian processes regression.

Background and aims: The quantitative retrieval of soil organic carbon (SOC) storage, particularly for soils with a large potential for carbon sequestration, is of global interest due to its link with the carbon cycle and the mitigation of climate change. However, complex ecosystems with good soil qualities for SOC storage are poorly studied. Methods: The interrelation between SOC and various vegetation remote sensing drivers is understood to demonstrate the link between the carbon stored in the vegetation layer and SOC of the top soil layers. Based on the mapping of SOC in two horizons (0-30 cm and 30-60 cm) we predict SOC with high accuracy in the complex and mountainous heterogeneous páramo system in Ecuador. A large SOC database (in weight % and in Mg/ha) of 493 and 494 SOC sampling data points from 0-30 cm and 30-60 cm soil profiles, respectively, were used to calibrate GPR models using Sentinel-2 and GIS predictors (i.e., Temperature, Elevation, Soil Taxonomy, Geological Unit, Slope Length and Steepness (LS Factor), Orientation and Precipitation). Results: In the 0-30 cm soil profile, the models achieved a R2 of 0.85 (SOC%) and a R2 of 0.79 (SOC Mg/ha). In the 30-60 cm soil profile, models achieved a R2 of 0.86 (SOC%), and a R2 of 0.79 (SOC Mg/ha). Conclusions: The used Sentinel-2 variables (FVC, CWC, LCC/Cab, band 5 (705 nm) and SeLI index) were able to improve the estimation accuracy between 3-21% compared to previous results of the same study area. CWC emerged as the most relevant biophysical variable for SOC prediction. Supplementary Information: The online version contains supplementary material available at 10.1007/s11104-022-05506-1.

Evaluating the Potential of Polygenic Risk Score to Improve Colorectal Cancer Screening.

BACKGROUND: Colorectal cancer has high incidence and associated mortality worldwide. Screening programs are recommended for men and women over 50. Intermediate screens such as fecal immunochemical testing (FIT) select patients for colonoscopy with suboptimal sensitivity. Additional biomarkers could improve the current scenario. METHODS: We included 2,893 individuals with a positive FIT test. They were classified as cases when a high-risk lesion for colorectal cancer was detected after colonoscopy, whereas the control group comprised individuals with low-risk or no lesions. 65 colorectal cancer risk genetic variants were genotyped. Polygenic risk score (PRS) and additive models for risk prediction incorporating sex, age, FIT value, and PRS were generated. RESULTS: Risk score was higher in cases compared with controls [per allele OR = 1.04; 95% confidence interval (CI), 1.02-1.06; P < 0.0001]. A 2-fold increase in colorectal cancer risk was observed for subjects in the highest decile of risk alleles (≥65), compared with those in the first decile (≤54; OR = 2.22; 95% CI, 1.59-3.12; P < 0.0001). The model combining sex, age, FIT value, and PRS reached the highest accuracy for identifying patients with a high-risk lesion [cross-validated area under the ROC curve (AUROC): 0.64; 95% CI, 0.62-0.66]. CONCLUSIONS: This is the first investigation analyzing PRS in a two-step colorectal cancer screening program. PRS could improve current colorectal cancer screening, most likely for higher at-risk subgroups. However, its capacity is limited to predict colorectal cancer risk status and should be complemented by additional biomarkers. IMPACT: PRS has capacity for risk stratification of colorectal cancer suggesting its potential for optimizing screening strategies alongside with other biomarkers.

Medial Temporal Lobe Involvement in Human Prion Diseases: Implications for the Study of Focal Non Prion Neurodegenerative Pathology.

Human prion and non-prion neurodegenerative diseases share pathogenic mechanisms and neuropathological features. The lesion profile of a particular entity results from specific involvement of vulnerable neuron populations and connectivity circuits by a pathogenic protein isoform with strain-like properties. The lesion profile of the medial temporal lobe (MTL) was studied in postmortem tissue of 143 patients with human prion disease (HPD) including sporadic, genetic, and acquired forms. Most cases (90%) were classified according to PrPres type and/or PRNP codon 129 status, in addition to a full neuropathological profile. Mixed histotypes represented 29.4% of total sporadic Creutzfeldt-Jakob disease (sCJD) cases. An intensity score of involvement including spongiosis and astrogliosis was determined for the amygdala, presubiculum, subiculum, entorhinal cortex, CA1 to CA4 sectors of the hippocampal cortex, and dentate gyrus. Connectivity hubs within the MTL presented the highest scores. Diverse lesion profiles were obtained for different types and subtypes of HPD. Impact of mixed PrPres types on the MTL lesion profile was higher for sCJDMV2K cases than in other histotypes. Differences between MTL profiles was globally consistent with current evidence on specific strains in HPD. These results may be relevant for the analysis of possible strain effects in focal non-prion neurodegenerative conditions limited to the MTL.

Pendulum tuned mass damper: optimization and performance assessment in structures with elastoplastic behavior.

Different types of tuned mass dampers (TMD) have been applied to reduce wind and seismic induces vibrations in buildings. We analyze a pendulum tuned mass damper (PTMD) to reduce vibrations of structures that exhibit elastoplastic behavior subjected to ground motion excitation. Using a simple dynamic model of the primary structure with and without the PTMD and a random process description of the ground acceleration, the performance improvement of the structure is assessed using statistical linearization. The Liapunov equation is used to estimate the mean-square response in the stationary condition of the random process and optimize PTMD parameters. The optimum values of the PTMD frequency and damping ratio are defined as PTMD design values for a specific maximum seismic intensity design criterion. The results show that: (1) The values of the PTMD effectiveness criterion and the optimal design values of the frequency ratio are higher when the damping ratio of the primary structure decreases. (2) The performance of the optimized PTMD is higher when the structure exhibits a linear hysteresis loop (low seismic intensity). (3) The optimized PTMD controls the development of structural plasticity reducing vulnerability. (4) There is a strong dependence of the optimum PTMD parameters on the dynamic soil properties of the building foundation. (5) The PTMD performance improves as its mass increases. The optimum frequency ratio decreases, and the damping ratio increases as the mass of the pendulum increases. The PTMD designed and optimized with the proposed methodology reduces vibrations, controls the development of plasticity, and protects the primary structure, particularly in low and medium-intensity earthquakes.

Multi-predictor mapping of soil organic carbon in the alpine tundra: a case study for the central Ecuadorian páramo.

BACKGROUND: Soil organic carbon (SOC) affects essential biological, biochemical, and physical soil functions such as nutrient cycling, water retention, water distribution, and soil structure stability. The Andean páramo known as such a high carbon and water storage capacity ecosystem is a complex, heterogeneous and remote ecosystem complicating field studies to collect SOC data. Here, we propose a multi-predictor remote quantification of SOC using Random Forest Regression to map SOC stock in the herbaceous páramo of the Chimborazo province, Ecuador. RESULTS: Spectral indices derived from the Landsat-8 (L8) sensors, OLI and TIRS, topographic, geological, soil taxonomy and climate variables were used in combination with 500 in situ SOC sampling data for training and calibrating a suitable predictive SOC model. The final predictive model selected uses nine predictors with a RMSE of 1.72% and a R2 of 0.82 for SOC expressed in weight %, a RMSE of 25.8 Mg/ha and a R2 of 0.77 for the model in units of Mg/ha. Satellite-derived indices such as VARIG, SLP, NDVI, NDWI, SAVI, EVI2, WDRVI, NDSI, NDMI, NBR and NBR2 were not found to be strong SOC predictors. Relevant predictors instead were in order of importance: geological unit, soil taxonomy, precipitation, elevation, orientation, slope length and steepness (LS Factor), Bare Soil Index (BI), average annual temperature and TOA Brightness Temperature. CONCLUSIONS: Variables such as the BI index derived from satellite images and the LS factor from the DEM increase the SOC mapping accuracy. The mapping results show that over 57% of the study area contains high concentrations of SOC, between 150 and 205 Mg/ha, positioning the herbaceous páramo as an ecosystem of global importance. The results obtained with this study can be used to extent the SOC mapping in the whole herbaceous ecosystem of Ecuador offering an efficient and accurate methodology without the need for intensive in situ sampling.

Concomitant Acute Tubular Necrosis and Acute Interstitial Nephritis Induced by Tipifarnib in a Patient with Squamous Cell Carcinoma of the Lung.

Tipifarnib is a novel targeted treatment for hematologic malignancies that is being recently studied for the treatment of advanced solid organ tumors with HRAS mutations. There have been scarce reports on kidney adverse events in initial phase I and II trials. We present a case of acute kidney injury in a patient that had started treatment with tipifarnib for advanced squamous cell carcinoma of the lung. Kidney biopsy revealed acute tubular necrosis together with acute interstitial nephritis. Tipifarnib was discontinued and the patient was started with high-dose corticosteroids with an early taper completing a five-week steroid course, with full recovery of kidney function.

Homoisoflavanones from Agave tequilana Weber.

Three homoisoflavanones were isolated from the "piña" and leaves of Agave tequilana Weber. The compounds were identified as: 5,7-dihydroxy-3-(4-methoxybenzyl)-chroman-4-one (1), 7-hydroxy-3-(4-hydroxybenzyl)-chroman-4-one (2) and 4'-demethyl-3,9-dihydro-punctatin (3). This is the first phytochemical study carried out to Agave tequilana Weber.

Evaluating the conservation state of the páramo ecosystem: An object-based image analysis and CART algorithm approach for central Ecuador.

Ecuadorian páramo ecosystems (EPEs) function as water sources, contain large soil carbon stores and high levels of biodiversity, and support human populations. The EPEs are mainly herbaceous páramo (HP). To inform policy and management and help drive ecological science toward a better understanding of the HP ecosystem, and the relationships among its multiple ecosystem services, we asked: (1) What is the state of the HP regarding its land use/land cover (LULC)?; and (2) Is the HP being pushed away from its natural state or it is regenerating? To answer these questions, we assessed the LULC in central EPEs using Landsat 8 imagery, Object-Based Image Analysis (OBIA) and a Classification and Regression Trees (CART) algorithm. Results show that two-fifths of the paramo ecosystem remain as native HP (NHP) and two-fifths as anthropogenic HP (AHP). Although the anthropic alteration of the pedogenesis of young paramo soil leads to the establishment of AHP, we found evidence of regeneration and resilience of the NHP. The results of this study will be useful to scientists and decision-makers with interest in páramo ecosystems in central Ecuador. The proposed methodology is simple, fast, and could be implemented in other landscapes to establish comprehensive monitoring systems useful in landscape assessment and planning.

Differences in virological response to pegylated interferon and ribavirin between hepatitis C virus (HCV)-monoinfected and HCV-HIV-coinfected patients.

BACKGROUND: Suboptimal doses of ribavirin have been suggested to explain the diminished efficacy of pegylated interferon (PEG-IFN) plus ribavirin in hepatitis C virus (HCV)-HIV-coinfected patients. METHODS: A cohort of 104 coinfected patients and an age-, sex- and genotype-matched cohort of HCV-monoinfected patients (n = 104) were compared. All patients received PEG-IFN-alpha2a 180 microg/week plus ribavirin 800-1,200 mg daily (HCV genotype 2/3 patients received 800 mg daily and those with genotype 1/4 received 1,000-1,200 mg daily) for 48 weeks (24 weeks for monoinfected patients with genotypes 2/3). HCV RNA levels were determined qualitatively at weeks 4, 12, 24, 48 and 72 and quantified monthly until week 12. RESULTS: The coinfected cohort had more advanced liver disease and lower body weight. HCV genotype 1 patients coinfected with HIV showed higher levels of HCV RNA than monoinfected patients. A significantly higher proportion of coinfected patients interrupted the prescribed treatment period prematurely (84% versus 98%). During the first 12 weeks, smaller decreases in HCV RNA levels were observed in coinfected patients. Among patients with HCV genotype 1, coinfected patients achieved lower rates of early virological response (64% versus 87%), end-of-treatment response (47.3% versus 80%) and sustained virological response (SVR; 27.3% versus 56.4%), but not rapid virological response (RVR). HCV-HIV-coinfected patients with HCV genotype 2/3 achieved significantly lower rates of RVR (52% versus 88%). Multivariate analysis identified RVR, gender and liver fibrosis as independent predictors of SVR. CONCLUSIONS: Differences in efficacy of PEG-IFN-alpha2a plus ribavirin treatment between HCV-HIV-coinfected and HCV-monoinfected patients were maintained despite optimized ribavirin dose.