Host space, not energy or symbiont size, constrains feather mite abundance across passerine bird species.

Comprehending symbiont abundance among host species is a major ecological endeavour, and the metabolic theory of ecology has been proposed to understand what constrains symbiont populations. We parameterized metabolic theory equations to investigate how bird species' body size and the body size of their feather mites relate to mite abundance according to four potential energy (uropygial gland size) and space constraints (wing area, total length of barbs and number of feather barbs). Predictions were compared with the empirical scaling of feather mite abundance across 106 passerine bird species (26,604 individual birds sampled), using phylogenetic modelling and quantile regression. Feather mite abundance was strongly constrained by host space (number of feather barbs) but not by energy. Moreover, feather mite species' body size was unrelated to the body size of their host species. We discuss the implications of our results for our understanding of the bird-feather mite system and for symbiont abundance in general.

Apremilast and biologics: Characteristics of patients treated with apremilast before, during, or after a biological treatment.

Apremilast is an oral small molecule approved for the treatment of psoriasis, psoriatic arthritis and oral ulcers associated with Behçet's disease. This research was conducted to describe the characteristics of patients who received treatment with apremilast for a skin disorder, either before, during, or after a biological treatment, with the aim of analyze the reasons that lead to start this drug in real clinical practice or suspend it for another. A total of 41 patients were enrolled: nine (22.0%) had received biological treatment prior to apremilast, seven (17.0%) both before and after apremilast and 25 (61.0%) after apremilast. One patient received concomitant treatment with adalimumab and apremilast. Most patients (85.4%) received apremilast as treatment for psoriasis. Reasons for starting apremilast were lack of efficacy with previous treatments (85.4%) and adverse effects or contraindication to previous treatments (14.6%), without statistically significant differences between patients who had received a previous biologic and those who had not. Drug survival was not influenced by previous biological treatment, but we found an increased risk of drug discontinuation in patients with chronic kidney disease (log-rank p = 0.028). The main reason of apremilast withdrawal was lack of adequate disease control (60.0%), most of whom required treatment with biologics. Therefore, despite the extensive development of new therapies for psoriasis and other dermatological conditions, apremilast is a widely used drug even in patients who are candidates for biologic treatment. Its initiation is more frequent due to poor disease control than because of other therapies contraindications.

Differential survival throughout the full annual cycle of a migratory bird presents a life-history trade-off.

Long-distance migrations are among the most physically demanding feats animals perform. Understanding the potential costs and benefits of such behaviour is a fundamental question in ecology and evolution. A hypothetical cost of migration should be outweighed by higher productivity and/or higher annual survival, but few studies on migratory species have been able to directly quantify patterns of survival throughout the full annual cycle and across the majority of a species' range. Here, we use telemetry data from 220 migratory Egyptian vultures Neophron percnopterus, tracked for 3,186 bird months and across approximately 70% of the species' global distribution, to test for differences in survival throughout the annual cycle. We estimated monthly survival probability relative to migration and latitude using a multi-event capture-recapture model in a Bayesian framework that accounted for age, origin, subpopulation and the uncertainty of classifying fates from tracking data. We found lower survival during migration compared to stationary periods (ß = -0.816; 95% credible interval: -1.290 to -0.318) and higher survival on non-breeding grounds at southern latitudes (<25°N; ß = 0.664; 0.076-1.319) compared to on breeding grounds. Survival was also higher for individuals originating from Western Europe (ß = 0.664; 0.110-1.330) as compared to further east in Europe and Asia, and improved with age (ß = 0.030; 0.020-0.042). Anthropogenic mortalities accounted for half of the mortalities with a known cause and occurred mainly in northern latitudes. Many juveniles drowned in the Mediterranean Sea on their first autumn migration while there were few confirmed mortalities in the Sahara Desert, indicating that migration barriers are likely species-specific. Our study advances the understanding of important fitness trade-offs associated with long-distance migration. We conclude that there is lower survival associated with migration, but that this may be offset by higher non-breeding survival at lower latitudes. We found more human-caused mortality farther north, and suggest that increasing anthropogenic mortality could disrupt the delicate migration trade-off balance. Research to investigate further potential benefits of migration (e.g. differential productivity across latitudes) could clarify how migration evolved and how migrants may persist in a rapidly changing world.

Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy.

Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival.From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding (p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34+/CD7+ and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment (p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival.In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.

Long-term results of linaclotide in the treatment of constipation-type irritable bowel syndrome.

BACKGROUND: constipation-predominant irritable bowel syndrome (C-IBS) is a prevalent, complex and multifactorial disorder that represents a challenge in terms of diagnosis and therapeutic management. OBJECTIVE: to evaluate the effectiveness, safety and treatment satisfaction of linaclotide in C-IBS patients. METHODS: prospective, single-center and observational study conducted in patients diagnosed with C-IBS. The patients were treated with linaclotide (Constella®, Allergan Inc., Irvine, CA), once-daily via an oral capsule of 290-µg, 30 minutes before breakfast. The primary effectiveness endpoint was the number of bowel movements per week. The secondary endpoints included treatment satisfaction and changes from baseline in frequency and severity of symptoms (abdominal pain and bloating). This was assessed via an 11-point visual analog scale (VAS) reported by the patients in a daily register. RESULTS: thirty female patients were consecutively included. The median follow-up time was 18 months. The mean (standard deviation [SD]) number of weekly bowel movements significantly increased from 0.9 (0.6) at baseline to 4.7 (3.9) at the end of follow-up, p < 0.0001. Abdominal pain significantly decreased from 5.7 (2.3) at baseline to 3.1 (2.8) at the end of the follow-up period, p < 0.0001. Similarly, bloating significantly decreased from 6.8 (1.6) to 2.9 (2.5) at the beginning and end of the treatment period, respectively, p < 0.0001. The mean (SD) degree of satisfaction at the end of the study was 6.7 (3.0). CONCLUSIONS: long-term linaclotide treatment in patients with C-IBS is effective and safe in the clinical setting.

Cannabinoids assessment in plasma and urine by high performance liquid chromatography-tandem mass spectrometry after molecularly imprinted polymer microsolid-phase extraction.

A molecularly imprinted polymer (MIP) selective for cannabinoids [Δ9-tetrahydrocannabinol (Δ9-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THC-COOH), and 11-hydroxy-Δ9-tetrahydrocannabinol (Δ9-THC-OH)] has been synthesized, fully characterized, and applied to the assessment of plasma and urine analysis of marijuana abuse by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Δ9-THC-COOH was used as a template molecule, whereas ethylene glycol dimethacrylate (EGDMA) was used as a functional monomer, divinylbenzene (DVB) as a cross-linker, and 2,2'-azobisisobutyronitrile (AIBN) as an initiator. The prepared MIP was found to be highly selective for cannabinoids typically found in blood and urine, and also for cannabinol (CBN) and cannabidiol (CBD). MIP beads (50 mg) were loaded inside a cone-shaped device made of a polypropylene (PP) membrane for microsolid-phase extraction (µ-SPE) in batch mode. Optimum retention of analytes (0.1 to 1.0 mL of plasma/urine) was achieved by fixing plasma/urine pH at 6.5 and assisting the procedure by mechanical shaking (150 rpm, 40 °C, 12 min). Optimum elution conditions implied 2 mL of a 90:10 methanol/acetic acid and ultrasound extraction (35 kHz, 325 W) for 6 min. Good precision was assessed by intra-day and inter-day assays. In addition, the method was found to be accurate after intra-day and inter-day analytical recovery assays and after analyzing control serum and urine control samples. The limits of quantification were in the range of 0.36-0.49 ng L-1 (plasma analysis) and 0.47-0.57 ng L-1 (urine analysis). These values are low enough for confirmative conclusions regarding marijuana abuse through blood and urine analysis. Graphical Abstract ᅟ.

Fibro-Osseous Pseudotumor of the Digits Mimicking Pyogenic Granuloma.

Fibro-osseous pseudotumor of the digits is a benign neoplasm that originates in the soft tissue adjacent to the short bones of the hands and feet. We present a case in a 13-year-old girl that was initially misdiagnosed as pyogenic granuloma. Familiarity with this entity and imaging and histologic studies are necessary to avoid incorrect diagnoses and aggressive surgical interventions.

Simple and Sensitive Molecularly Imprinted Polymer - Mn-Doped ZnS Quantum Dots Based Fluorescence Probe for Cocaine and Metabolites Determination in Urine.

A new molecularly imprinted polymer (MIP)-based fluorescent artificial receptor has been prepared by anchoring a selective MIP for cocaine (COC) on the surface of polyethylene glycol (PEG) modified Mn-doped ZnS quantum dots (QDs). The prepared material combines the high selectivity attributed to MIPs and the sensitive fluorescent property of the Mn-doped ZnS QDs. Simple and low cost methods have therefore been optimized for assessing cocaine abuse in urine by monitoring the fluorescence quenching when the template (COC) and also metabolites from COC [benzoylecgonine (BZE) and ecgonine methyl ester (EME)] are present. Fluorescence quenching was not observed when performing experiments with other drugs of abuse (and their metabolites) or when using nonimprinted polymer (NIP)-coated QDs. Under optimized operating conditions (1.5 mL of 200 mg L(-1) MIP-coated QDs solution, pH 5.5, and 15 min before fluorescence scanning) two analytical methods were developed/validated. One of the procedures (direct method) consisted of urine sample 1:20 dilution before fluorescence measurements. The method has been found to be fast, precise, and accurate, but the standard addition technique for performing the analysis was required because of the existence of matrix effect. The second procedure performed a solid phase extraction (SPE) first, avoiding matrix effect and allowing external calibration. The limits of detection of the methods were 0.076 mg L(-1) (direct method) and 0.0042 mg L(-1) (SPE based method), which are lower than the cutoff values for confirmative conclusions regarding cocaine abuse.

Solid phase microextraction and gas chromatography-mass spectrometry methods for residual solvent assessment in seized cocaine and heroin.

A simple sample pre-treatment method based on solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) has been optimized and validated for the assessment of 15 residual solvents (2-propanol, 2-methylpentane, 3-methylpentane, acetone, ethyl acetate, benzene, hexane, methylcyclohexane, methylcyclopentane, m-xylene, propyl acetate, toluene, 1,2,4-trimethylbenzene, dichloromethane, and ethylbenzene) in seized illicit cocaine and heroin. DMSO and DMF as sample diluents were found to offer the best residual solvent transference to the head space for further adsorption onto the SPME fiber, and the developed method therefore showed high sensitivity and analytical recovery. Variables affecting SPME were fully evaluated by applying an experimental design approach. Best conditions were found when using an equilibration time of 5 min at 70 °C and headspace sampling of residual solvents at the same temperature for 15 min. Method validation, performed within the requirements of international guidelines, showed excellent sensitivity, as well as intra- and inter-day precision and accuracy. The proposed methodology was applied to 96 cocaine samples and 14 heroin samples seized in Galicia (northwestern Spain) within 2013 and 2014.

Preserved brains from the Spanish Civil War mass grave (1936) at La Pedraja1, Burgos, Spain.

During the excavation of the Spanish Civil War mass grave at La Pedraja (Burgos, Spain), 104 individuals were found interred within it, 45 of which displayed brains that were preserved but dehydrated and reduced in size. This exceptional finding has resulted in the formation of a multidisciplinary team, with the aim of obtaining as much information as possible and to primarily understand the taphonomic phenomena that has led to the preservation of these brains. The following types of analyses were undertaken on three of these brains: macroscopy, histology, radiology, chemical-toxicology, genetics, chemical analysis of the soil and 3D modelling for stereolithography. The historical context was considered, plus all archaeological and other forensic data provided by the investigation of the mass grave. The results of the analyses on these morphologically identifiable human brains confirmed the presence of nerve structures, fatty acids, and in one case ante-mortem evidence for an intracranial haemorrhage. The fatty acid profile corresponds to the process of saponification. Therefore, the interpretation is that the preservation of these brains at the mass grave of La Pedraja was due to the saponification process, which was influenced by the manner and cause of death, the chemical composition of the brain, the physicochemical properties of the soil and the meteorological conditions at the time.

Determination of direct alcohol markers: a review.

Alcohol is the most popular legal drug used in our society today, and its consumption by pregnant women remains an important public health problem. Gestational alcohol consumption can result in a continuum of adverse fetal outcomes known as fetal alcohol spectrum disorder (FASD). Effective strategies are needed to prevent the increasing adoption of risky drinking behaviors. Because ethanol itself is only measurable for a few hours after ethanol intake in conventional matrices including blood, urine, and sweat, these matrices are only useful to detect recent ethanol exposure. Since approximately early 2000, the non-oxidative ethanol metabolites have received increasing attention because of their specificity and, in some cases, wide time window of detection in non-conventional matrices including hair and meconium. In the attempt to update analytical methods for the determination of non-oxidative markers of alcohol, the objective of this study is to review published studies that measure fatty-acid ethyl esters (FAEE), ethyl glucuronide (EtG), and phosphatidylethanol (PEth) in alternative biological matrices, focusing on the extraction and detection methods and full analytical conditions used.

Rapid determination of quetiapine in blood by gas chromatography-mass spectrometry. Application to post-mortem cases.

A simple, fast and sensitive method for the determination of quetiapine in human blood has been developed and validated. The method involved a basic liquid-liquid extraction procedure and subsequent analysis by gas chromatography-mass spectrometry, previous derivatization with bis(trimethylsilyl)-trifluoro-acetamide and chorotrimethylsilane (99 : 1). The methods of validation included linearity with a correlation coefficient > 0.99 over the range 0.02-1 µg ml(-1), intra- and interday precision (always < 12%) and accuracy (mean relative error always < 12%) to meet the bioanalytical acceptance criteria. The limit of detection was 0.005 µg ml(-1). The procedure was further applied to post mortems from the Institute of Legal Medicine, University of Santiago de Compostela.

MR imaging in the evaluation of cystic-appearing soft-tissue masses of the extremities.

Cystic-appearing lesions are commonly seen in clinical practice at imaging of the extremities. However, only some of these lesions are truly cystic lesions (eg, ganglia or synovial cysts, bursae) and may be managed conservatively. Fluid-filled lesions usually have homogeneous high T2 signal at magnetic resonance (MR) imaging. A broad array of solid benign masses (eg, myxomas, peripheral nerve sheath tumors [PNSTs], certain vascular lesions, glomus tumors) and malignant solid masses (including undifferentiated pleomorphic sarcomas, myxofibrosarcomas, myxoid liposarcomas, synovial sarcomas, extraskeletal myxoid chondrosarcomas, and, less frequently, soft-tissue metastases) may also exhibit bright T2 signal at MR imaging, thereby simulating a cyst. On the other hand, fluid-filled lesions with associated complications (eg, bleeding or inflammatory changes) may have a more complex appearance. MR imaging plays a major role in distinguishing truly cystic lesions from solid lesions. If a cystic-appearing lesion demonstrates wall thickening or internal complexity (heterogeneous signal, nodules, or thick septa), evaluation with contrast material enhancement is mandatory, and a solid lesion must be suspected if any internal enhancement is present. In addition to categorizing the lesions as truly cystic or solid, the differential diagnosis may be further narrowed by considering the anatomic location of the lesion or characteristic imaging features (eg, internal linear or patchy enhancement at contrast-enhanced MR imaging and an intramuscular location in myxomas; the "split fat sign," "string sign," and "target sign" in PNSTs; tiny foci of fat in myxoid liposarcomas). In most cases, however, histologic analysis is required to achieve a definitive diagnosis.

Optimization of microwave-assisted extraction of analgesic and anti-inflammatory drugs from human plasma and urine using response surface experimental designs.

The performance of microwave-assisted extraction and HPLC with photodiode array detection method for determination of six analgesic and anti-inflammatory drugs from plasma and urine, is described, optimized, and validated. Several parameters affecting the extraction technique were optimized using experimental designs. A four-factor (temperature, phosphate buffer pH 4.0 volume, extraction solvent volume, and time) hybrid experimental design was used for extraction optimization in plasma, and three-factor (temperature, extraction solvent volume, and time) Doehlert design was chosen to extraction optimization in urine. The use of desirability functions revealed the optimal extraction conditions as follows: 67°C, 4 mL phosphate buffer pH 4.0, 12 mL of ethyl acetate and 9 min, for plasma and the same volume of buffer and ethyl acetate, 115°C and 4 min for urine. Limits of detection ranged from 4 to 45 ng/mL in plasma and from 8 to 85 ng/mL in urine. The reproducibility evaluated at two concentration levels was less than 6.5% for both specimens. The recoveries were from 89 to 99% for plasma and from 83 to 99% for urine. The proposed method was successfully applied in plasma and urine samples obtained from analgesic users.

Isolation and quantification of synthetic cannabinoid receptor agonists in human urine using membrane-assisted solvent extraction followed by liquid chromatography-tandem mass spectrometry.

The global market for new psychoactive substances (NPSs) continues to expand, and the range of drugs available on the market has probably never been wider. Synthetic cannabinoids (SCRAs) constitute the largest family of NPSs, and they go unnoticed during illicit drug market control and during routine toxicological-forensic analysis. Membrane-assisted solvent extraction (MASE) has been a novelty proposed for the simultaneous extraction of SCRAs, and urine has been selected as a model forensic-clinical sample. Isolated SCRAs were further determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). An optimised sample pre-treatment procedure consists of using 400 µL of n-hexane as an extraction phase placed inside a polypropylene (PP) membrane, adjusting the donor phase (urine) at a pH value of 5.9. Extraction was assisted by mechanical (orbital-horizontal) stirring in a temperature-controlled chamber at room temperature for 20 min. n-Hexane extracts were evaporated to dryness and re-suspended in 100 µL of mobile phase, which leads to a pre-concentration factor of 50. Method validation showed analytical recoveries higher than 80% for most SCRAs and repeatability (inter-day and intra-day assays) with RSD values lower than 20%. The proposed method was found to be selective and sensitive and limits of quantification (LOQs) between 0.10 and 1.0 µg L-1 were achieved.

Ultrasound assisted membrane-assisted solvent extraction for the simultaneous assessment of some drugs involved in drug-facilitated sexual assaults by liquid chromatography-tandem mass spectrometry.

A simple and highly efficient ultrasound assisted membrane-assisted solvent extraction (MASE) pre-treatment method for urine has been developed and validated for the simultaneous determination of twenty-two drugs involved in drug-facilitated sexual assaults (DFSAs) by liquid chromatography-tandem mass spectrometry. MASE was performed with 4.0 mL of urine (pH adjusted at 12), 400 µL of hexane as an organic solvent inside the polypropylene membrane, and ultrasonication (45 kHz, 120 W) for 10 min. A pre-concentration factor of 40 was achieved after evaporation (N2 stream) and re-dissolution in 100 µL of methanol. Analytes were separated using a Zorbax Eclipse Plus C18 column under gradient elution with aqueous 10 mM NH4HCO3 (pH 8.0) and methanol as mobile phases. Matrix-matched calibrations allowed the assessment of DFSA drugs of quite different octanol-water partition coefficients (Ko/w), from 1.32 101 for pregabalin to 2.45 105 for clomipramine (Log P values from 1.12 (pregabalin) to 5.39 (clomipramine)). The limit of detection (LOD) was between 0.0075 to 0.37 µg L-1, with analytical recoveries ranging from 73 to 103%, and relative standard deviations (RSDs) within the 2-20% range. The applicability of the method was demonstrated after analysing urine samples under forensic investigation.

The variability of juvenile dispersal in an opportunistic raptor.

The juvenile dispersal of raptors is a crucial stage that stretches from parental independence to the establishment of the first breeding area. Between 2012 and 2020, 44 juvenile red kites Milvus milvus from the Spanish breeding population were tagged using GPS telemetry to study their dispersal. Juveniles left the parental breeding area at the end of their first summer and performed wandering movements throughout the Iberian Peninsula, returning to the parental breeding area the following year, repeating the same pattern until they settled in their first breeding area. We analyzed the mean distance from the nest, the maximum reached distances, and the traveled distances (daily and hourly) during the first 2 years of dispersal and compared them. Despite the high individual variability, variables describing the dispersal movements of juveniles showed a decreasing trend during the second dispersal year: 80% of individuals reached a shorter maximum distance in the second year, 70% decreased their mean distance to the nest, 65% decreased their hourly traveled distances, and 50% decreased their daily traveled distances. On the other hand, the red kites usually combined wandering movements with the establishment of temporary settlement areas (TSA). The average duration of settlement in the TSAs was 75 ± 40 days (up to 182 days) and was located at 182 ± 168 km from the nest. In those areas, juveniles used 781.0 ± 1895.0 km2 (KDE 95%). Some of the TSAs were used by several individuals, which suggests that these areas might be good targets for conservation in future management plans.

Prognostic Value of Measurable Residual Disease in Patients with AML Undergoing HSCT: A Multicenter Study.

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the best therapeutic option for many patients with acute myeloid leukemia (AML). However, relapse remains the main cause of mortality after transplantation. The detection of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in AML, before and after HSCT, has been described as a powerful predictor of outcome. Nevertheless, multicenter and standardized studies are lacking. A retrospective analysis was performed, including 295 AML patients undergoing HSCT in 4 centers that worked according to recommendations from the Euroflow consortium. Among patients in complete remission (CR), MRD levels prior to transplantation significantly influenced outcomes, with overall (OS) and leukemia free survival (LFS) at 2 years of 76.7% and 67.6% for MRD-negative patients, 68.5% and 49.7% for MRD-low patients (MRD < 0.1), and 50.5% and 36.6% for MRD-high patients (MRD ≥ 0.1) (p < 0.001), respectively. MRD level did influence the outcome, irrespective of the conditioning regimen. In our patient cohort, positive MRD on day +100 after transplantation was associated with an extremely poor prognosis, with a cumulative incidence of relapse of 93.3%. In conclusion, our multicenter study confirms the prognostic value of MRD performed in accordance with standardized recommendations.