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Abstract Background There are currently no models for the transition of patients with metabolic bone diseases (MBDs) from paediatric to adult care. The aim of this project was to analyse information on the experience of physicians in the transition of these patients in Spain, and to draw up consensus recommendations with the specialists involved in their treatment and follow-up. Methods The project was carried out by a group of experts in MBDs and included a systematic review of the literature for the identification of critical points in the transition process. This was used to develop a questionnaire with a total of 48 questions that would determine the degree of consensus on: (a) the rationale for a transition programme and the optimal time for the patient to start the transition process; (b) transition models and plans; (c) the information that should be specified in the transition plan; and (d) the documentation to be created and the training required. Recommendations and a practical algorithm were developed using the findings. The project was endorsed by eight scientific societies. Results A total of 86 physicians from 53 Spanish hospitals participated. Consensus was reached on 45 of the 48 statements. There was no agreement that the age of 12 years was an appropriate and feasible point at which to initiate the transition in patients with MBD, nor that a gradual transition model could reasonably be implemented in their own hospital. According to the participants, the main barriers for successful transition in Spain today are lack of resources and lack of coordination between paediatric and adult units. Conclusions The TEAM Project gives an overview of the transition of paediatric MBD patients to adult care in Spain and provides practical recommendations for its implementation.

Study Design Case-control study. Purpose Analyze association between imaging factors related to the failure of conservative treatment in isolated subaxial cervical facet fractures. Overview of Literature Facet fracture (F1, F2, and F3 AOSpine) may be stable or unstable depending on clinical and imaging variables, which are not well established. As a result, differences in fracture management lead to differences in surgical or conservative indications, and there is no evidence to predict conservative treatment failure. Methods Patients were categorized into two groups: six patients (16.2%) with conservative treatment failure (defined as the appearance of neurological symptoms, listhesis >3.5 mm, kyphotic deformation >11°, and/or non-union), and 31 patients (83.7%) with successful conservative management (defined as complete consolidation confirmed by computed tomography [CT] at the 6-month follow-up). All participants were fitted with rigid collars of the Miami type, and standardized follow-up was performed until consolidation or failure. CT and magnetic resonance imaging (MRI) was used to examine imaging characteristics. Sagittal balance parameters were assessed using CT, and signs of acute disc injury, prevertebral edema, facet synovitis, and interspinous hyperintense signal were assessed using MRI. Results Thirty-seven patients were diagnosed with unilateral cervical facet fractures between 2009 and 2020. In this sample, acute disc injury had a significative association to failure of conservative treatment in F2 and F3 AOSpine facet fractures, 100% of the failure group presented with traumatic disc injury compared to 9.7% of the successful group, for the other variables: prevertebral edema, 83.7% vs. 41.9%; facet synovitis, 100% vs. 77.4%; and interspinous hyperintensity, 71.4% vs. 38.7%, respectively. With conservative management, all F1 fractures healed successfully. Conservative treatment failed in 20% of F2 fractures and 50% of F3 fractures, respectively. In terms of cervical sagittal balance parameters, there were no significant differences between groups. Conclusions Conservative management was successful in all F1 fractures. In F2 and F3 types, there was a significant association between acute disc injury and conservative treatment failure.

Abstract Background Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. Results Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). Conclusions Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.

Abstract Anopheles darlingi is the main malarial vector in the Brazilian Amazon region. An. nuneztovari s.l., An. triannulatus s.l., An. evansae, and An. benarrochi s.l. do not have a defined role as malarial vectors, although they have been found to be naturally infected with Plasmodium vivax, and some develop oocysts. In this study, we evaluated the importance of low numbers of oocysts in sporozoite salivary gland invasion and transmission. Field-collected mosquitoes were experimentally infected with P. vivax. The infection rates and oocyst and sporozoite infection intensities were evaluated and compared with those of An. aquasalis. We found the highest number of oocysts in An. darlingi (mean = 39.47) and the lowest in An. nuneztovari s.l. (mean = 2). The highest number of sporozoites was observed in An. darlingi (mean = 610) and lowest in An. benarrochi s.l. (mean = 30). Plasmodium vivax DNA was detected in the saliva of all mosquito species after a blood meal. Regardless of the number of oocysts, all species transmitted sporozoites during blood meals. Considering the abundance of these mosquitoes and transmission of sporozoites, it is logical to assume that An. nuneztovari s.l. and An. triannulatus s.l. are involved in the transmission of P. vivax.

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ABSTRACT Objective: Cytological analysis and Bethesda classification of thyroid nodules is the standard method of diagnosing differentiated thyroid carcinoma (DTC). However, even for nodules with a non-malignant cytological diagnosis, there is a not insignificant risk of cancer. There are doubts whether this lack of certainty would influence patient prognosis. Our aim was to compare patients with DTC, classified according to the preoperative cytological diagnosis, regarding their evolution. Subjects and methods: A retrospective study was carried out with 108 DTC patients submitted to total thyroidectomy (TT) between 2009 and 2015, divided into three groups according to preoperative cytological diagnosis (Bethesda classification): classes I/II, III/IV, and V/VI. Groups were compared for evolution considering response to treatment at last evaluation as well as time disease free. Statistical analysis used ANOVA, chi squared, and Kaplan-Meier curves with p

Abstract The grey wolf (Canis lupus) persists in a variety of human-dominated landscapes and is subjected to various legal management regimes throughout Europe. Our aim was to assess the effects of intrinsic and methodological determinants on the hair cortisol concentration (HCC) of wolves from four European populations under different legal management. We determined HCC by an enzyme-linked immune assay in 259 hair samples of 133 wolves from the Iberian, Alpine, Dinaric-Balkan, and Scandinavian populations. The HCC showed significant differences between body regions. Mean HCC in lumbar guard hair was 11.6 ± 9.7 pg/mg (range 1.6–108.8 pg/mg). Wolves from the Dinaric-Balkan and Scandinavian populations showed significantly higher HCC than Iberian wolves, suggesting that harvest policies could reflected in the level of chronic stress. A significant negative relationship with body size was found. The seasonal, sex and age patterns are consistent with other studies, supporting HCC as a biomarker of chronic stress in wolves for a retrospective time frame of several weeks. Our results highlight the need for standardization of sampling and analytical techniques to ensure the value of HCC in informing management at a continental scale.

ABSTRACT Objective: Our aim was to assess the ability of serum magnesium (Mg), measured on the first postoperative day (Mg1PO), to predict the need for calcium (Ca) replacement in patients undergoing total thyroidectomy (TT). Subjects and methods: Eighty patients undergoing TT, with Mg1PO and PTH dosage in the first (PTH1h) and eighth (PTH8h) hours after TT, were evaluated for the need for Ca replacement. Data were evaluated by uni/multivariate logistic regression and Receiver Operating Characteristic (ROC) curve. Results: 32 patients (40%) required Ca replacement. Median PTH1h, PTH8h and Mg1PO were higher in the no replacement group: 17 versus (vs) 3 pg/mL (p < 0.001), 18.2 vs 3.0 pg/mL (p < 0.001) and 2 vs 1.6 mg/dL (p < 0.001), respectively. Mg1PO was the isolated predictor for this replacement (odds ratio = 0.0004, 95% confidence interval: 0.000003-0.04; p = 0.001), with the cut-off value of 1.8 mg/dL showing sensitivity and specificity of 78.1% and 87.5%, respectively. Conclusions: In this group of patients, serum Mg1PO was the isolated predictor for the need for Ca replacement.

Background: Aging is associated with a decrease in muscle mass. Insulin resistance and hyperglycemia accelerate muscle loss, leading to a deterioration in strength, muscle mass, and physical capacity in older adults. This study was conducted to determine the association between sarcopenia and poor glycemic control in older adults with type 2 diabetes mellitus (T2D). Methods: A cross-sectional study was carried out in older adults with T2D in geriatric outpatient clinics. Sarcopenia was diagnosed as per the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. According to glycosylated hemoglobin (HbA1c) levels, participants were classified into glycemic control (HbA1c ≤ 7.5%) and poor glycemic control (HbA1c ≥ 7.5%) groups. Results: Older adults with sarcopenia were found to have poor glycemic control compared to adults without sarcopenia (62.3% vs. 47.9%, p = 0.007). Logistic regression analysis showed an association between poor glycemic control and the presence of sarcopenia (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.17–2.75) and low muscle mass (OR: 1.73, 95% CI: 1.07–2.73). Conclusions: Poor glycemic control is associated with the presence of sarcopenia and low muscle mass, which highlights the need to implement better treatment strategies in order to reduce the loss of muscle mass.

Abstract REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) is a global strategy and regulation policy of the EU that aims to improve the protection of human health and the environment through the better and earlier identification of the intrinsic properties of chemical substances. It entered into force on 1st June 2007 (EC 1907/2006). REACH and EU policies plead for the use of robust high-throughput "omic" techniques for the in vitro investigation of the toxicity of chemicals that can provide an estimation of their hazards as well as information regarding the underlying mechanisms of toxicity. In agreement with the 3R’s principles, cultured cells are nowadays widely used for this purpose, where metabolomics can provide a real-time picture of the metabolic effects caused by exposure of cells to xenobiotics, enabling the estimations about their toxicological hazards. High quality and robust metabolomics data sets are essential for precise and accurate hazard predictions. Currently, the acquisition of consistent and representative metabolomic data is hampered by experimental drawbacks that hinder reproducibility and difficult robust hazard interpretation. Using the differentiated human liver HepG2 cells as model system, and incubating with hepatotoxic (acetaminophen and valproic acid) and non-hepatotoxic compounds (citric acid), we evaluated in-depth the impact of several key experimental factors (namely, cell passage, processing day and storage time, and compound treatment) and instrumental factors (batch effect) on the outcome of an UPLC-MS metabolomic analysis data set. Results showed that processing day and storage time had a significant impact on the retrieved cell's metabolome, while the effect of cell passage was minor. Meta-analysis of results from pathway analysis showed that batch effect corrections and quality control (QC) measures are critical to enable consistent and meaningful estimations of the effects caused by compounds on cells. The quantitative analysis of the changes in metabolic pathways upon bioactive compound treatment remained consistent despite the concurrent causes of metabolomic data variation. Thus, upon appropriate data retrieval and correction and by an innovative metabolic pathway analysis, the metabolic alteration predictions remained conclusive despite the acknowledged sources of variability.

ABSTRACT Objective: Thyrotropin-stimulated thyroglobulin (STg) after total thyroidectomy is a prognosis marker for differentiated thyroid carcinoma (DTC). As Tg level is influenced by thyrotropin (TSH), perhaps the STg/TSH ratio is also a prognosis marker for these tumours. We aimed to compare STg/TSH ratio and first STg level in differentiated thyroid carcinoma patients for their ability to predict the long-term response to initial treatment. Subjects and methods: This retrospective study evaluated data from 181 DTC patients for first (1st) STg and STg/TSH ratio, at 1-3 months post-total thyroidectomy and before iodine-131 therapy, according to response to initial therapy [Excellent/Indeterminate or Incomplete (Biochemical/Structural)] observed at final evaluation, and with the survival time with excellent/indeterminate response. Results: Cases with incomplete response presented higher STg level [225.13 ± 585.26 ng/mL versus (vs) 20.4 ± 192.9 ng/mL; p < 0.001] and STg/TSH ratio (3.01 ± 7.8 vs 0.27 ± 2.58; p < 0.001). Cutoffs of 5 ng/mL for STg and 0.085 for STg/TSH displayed sensitivities of 76.7% and 76.9%, and specificities of 79.2% and 82.6%, respectively, in predicting response to therapy. Values below these cutoffs were associated with longer survival time in excellent/indeterminate response (140.4 vs 15.9 and 144.6 vs 15.9 months, respectively). Conclusion: STg/TSH ratio has a similar performance to the 1st STg in predicting long-term response to initial therapy.

ABSTRACT Objective: Follicular lesions of the thyroid with papillary carcinoma nuclear characteristics are classified as infiltrative follicular variant of papillary thyroid carcinoma-FVPTC (IFVPTC), encapsulated/well demarcated FVPTC with tumour capsular invasion (IEFVPTC), and the newly described category “non-invasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) formerly known as non-invasive encapsulated FVPTC. This study evaluated whether computerized image analysis can detect nuclear differences between these three tumour subtypes. Materials and methods: Slides with histological material from 15 cases of NIFTP and 33 cases of FVPTC subtypes (22 IEFVPTC, and 11 IFVPTC) were analyzed using the Image J image processing program. Tumour cells were compared for both nuclear morphometry and chromatin textural characteristics. Results: Nuclei from NIFTP and IFVPTC tumours differed in terms of chromatin textural features (grey intensity): mean (92.37 ± 21.01 vs 72.99 ± 14.73, p = 0.02), median (84.93 ± 21.17 vs 65.18 ± 17.08, p = 0.02), standard deviation (47.77 ± 9.55 vs 39.39 ± 7.18; p = 0.02), and coefficient of variation of standard deviation (19.96 ± 4.01 vs 24.75 ± 3.31; p = 0.003). No differences were found in relation to IEFVPTC. Conclusion: Computerized image analysis revealed differences in nuclear texture between NIFTP and IFVPTC, but not for IEFVPTC.

Gambling is an international phenomenon, posing a serious threat to adolescents who begin gambling at a young age. This study aims, to explore gambling behavior in adolescents and interpret its risk factors. We conducted a three-waves cohort longitudinal study assessing gambling and associated risk factors in south-eastern Spain. Data were analyzed using the Capabilities, Opportunities, Motivations, Behavior (COM-B) model and the partial least squares path modelling (PLS-PM) technique. Gambling was measured by frequency and money spent; associated factors were knowledge about gambling, parental attitude towards gambling, risk perception, normative perception, and intention to gamble. These items were assigned as indicators of each construct of the COM-B model—capability, opportunity, motivation, and behavior—using the theoretical domains framework. Once the behavior was performed, feedback on future capability, opportunity, and motivation was observed. Results show that capability, determined by past experience, and opportunity, determined by parental attitudes, motivates adolescents to seek gambling experiences in the future. Identifying such factors that affect gambling behavior in adolescents and establishing relationships between them through a robust theoretical model is essential for designing effective interventions.

Objective: This study aimed to assess indications for surgical treatment, position of the ankle, time and rate of fusion after arthrodesis; to ascertain whether the technique provides fusion rates similar to those described in the published literature; and to quantify patients’ improvement according to the AOFA and VAS scores, and patients’ satisfaction using a Likert scale. Methods: This is a clinical study with a cohort of 18 patients (9 women and 9 men) with a mean age of 49.10 years, conducted from 2006 and 2016. Results: Post-traumatic arthrosis (88.88%), rheumatoid arthritis (5.56%), and Charcot-Marie-Tooth disease (5.56%) motivated the surgeries. Six ankles fused in an equinus position, and 12 of them in a neutral position. Five ankles fused in valgus angulation, and 13 in a neutral position. Five ankles fused in external rotation, 2 in internal rotation and 11 in a neutral position. In the postoperative period, American Orthopaedic Foot and Ankle Society (AOFAS) and visual analogue scale (VAS) scores showed an improvement of 31.6 points and 5.1 points, respectively. Regarding the Likert scale, 2 patients reported being very satisfied, 14 satisfied, and 2 partially satisfied. Conclusion: Fusion in a 100% of cases and patients’ overall satisfaction have led to the conclusion that this treatment method is appropriate to attain ankle fusion, with results similar to those found in the medical literature. Level of Evidence IV; Therapeutic Studies; Case Series.

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The World Health Organization estimates that the pandemic caused by the SARS-CoV-2 virus claimed more than 3 million lives in 2020 alone. This situation has highlighted the importance of vaccination programs and the urgency of working on new technologies that allow an efficient, safe, and effective immunization. From this perspective, nanomedicine has provided novel tools for the design of the new generation of vaccines. Among the challenges of the new vaccine generations is the search for alternative routes of antigen delivery due to costs, risks, need for trained personnel, and low acceptance in the population associated with the parenteral route. Along these lines, transdermal immunization has been raised as a promising alternative for antigen delivery and vaccination based on a large absorption surface and an abundance of immune system cells. These features contribute to a high barrier capacity and high immunological efficiency for transdermal immunization. However, the stratum corneum barrier constitutes a significant challenge for generating new pharmaceutical forms for transdermal antigen delivery. This review addresses the biological bases for transdermal immunomodulation and the technological advances in the field of nanomedicine, from the passage of antigens facilitated by devices to cross the stratum corneum, to the design of nanosystems, with an emphasis on the importance of design and composition towards the new generation of needle-free nanometric transdermal systems.

Introduction: DNA extracted from ancient human bones allows to analyze the genetic makeup of pre-Columbian populations and to determine the dynamics that gave rise to the diversity of contemporary populations. Objective: To determine the genetic diversity of skeletal remains associated with the Templo del Sol (Sun Temple) and their relationship with other contemporary and ancient communities of America. Materials and methods: We analyzed 13 individuals belonging to the pre-Columbian Muisca Period (IX-XVI centuries AD) from the vicinities of the Templo del Sol (Sun Temple) (Sogamoso, Boyacá) in the eastern Colombian Andes. Mitochondrial DNA was amplified and RFLPs were performed in order to type the four traditional Amerindian haplogroups (A, B, C and D). In addition, autosomal markers including amelogenin and Y-chromosome STRs were amplified. Results: Among the observed mitochondrial lineages, haplogroup A was the most frequent, followed by haplogroups B and C; no evidence of haplogroup D was found. The genetic variation analysis indicated a similar diversity of pre-Columbian Muiscas to that of contemporary populations belonging to the Chibcha linguistic family from Colombia and Central America. Molecular sexing was accomplished and it was compared to osteological data. With only one exception, anthropological and molecular data were consistent. Conclusions: Our results contribute new genetic elements supporting the hypothesis of Central American origin of the Chibcha groups of the Cundiboyacense plateau, and allowed sex typing and kinship evaluations.

Abstract In solitary carnivorous mammals, territoriality is assumed to benefit male fitness by ensuring the exclusivity of matings within territories via mate guarding and female defence. However, this hypothesis remains empirically untested. Here, we examined this hypothesis for solitary territorial carnivores using the Iberian lynx (Lynx pardinus) as a case study. We expected that territorial males sire all litters born within their territories, translating into the absence of multi-paternity cases within the same litter. We analysed parentage in 43 kittens, belonging to 20 different litters. For 42 kittens, a father could be assigned using microsatellites and always coincided with the individual holding the territory. For 16 kittens from 10 litters for which we also had information on SNPs, paternity assignments coincided with microsatellites, except for a litter (two kittens) from the same litter for which a different male was assigned, but the territorial male could not be excluded. Our results indicated that multi-paternity in the Iberian lynx must be a rare event, and that territorial males sire all litters born from the females with which they share territories. We propose that both the low number of mature individuals in the lynx population and the fact that female oestrus is induced by male presence may explain results.

Abstract Successful coexistence between large carnivores and humans is conditional upon effective mitigation of the impact of these species on humans, such as through livestock depredation. It is therefore essential for conservation practitioners, carnivore managing authorities, or livestock owners to know the effectiveness of interventions intended to reduce livestock predation by large carnivores. We reviewed the scientific literature (1990–2016), searching for evidence of the effectiveness of interventions. We found experimental and quasi-experimental studies were rare within the field, and only 21 studies applied a case-control study design (3.7% of reviewed publications). We used a relative risk ratio to evaluate the studied interventions: changing livestock type, keeping livestock in enclosures, guarding or livestock guarding dogs, predator removal, using shock collars on carnivores, sterilizing carnivores, and using visual or auditory deterrents to frighten carnivores. Although there was a general lack of scientific evidence of the effectiveness of any of these interventions, some interventions reduced the risk of depredation whereas other interventions did not result in reduced depredation. We urge managers and stakeholders to move towards an evidence-based large carnivore management practice and researchers to conduct studies of intervention effectiveness with a randomized case-control design combined with systematic reviewing to evaluate the evidence.

In music education, women are present in great numbers. In professional settings, however, women musicians are not as predominant. With some exceptions, such as Scandinavian countries, women still pursue gender equality in professional music practice. To inquire about the causes of this, we considered if gender-differences in amotivation in conservatoire instrument practice could be associated with aspects of learning environment. Self-determination theory (SDT) posits that learning environments may influence motivation, by satisfying or thwarting students' psychological needs and by selectively endorsing specific extrinsic goals. Thus, we analysed if-women and men-amotivation variations could be explained by differences in behavioural regulations and satisfaction of their psychological needs for competence and autonomy. Participants (67 women and 74 men, 18-47 years old) completed validated scales for amotivation, behavioural regulations, and needs satisfaction. Students exhibited high intrinsic and introjected regulations, and high autonomy and competence needs satisfaction. Students' identified regulation levels were modest, and external regulation and amotivation levels were low. Women students' perceived competence was lower, and their amotivation was higher than men's. Amotivation variations were explained positively by identified regulation and negatively by context-derived satisfaction of the psychological needs for competence (and autonomy, only among women). Results suggest that internalization of extrinsic goals can pose difficulties and that psychological needs satisfaction may counteract amotivation (autonomy being potentially more important for women musicians).

In a genetic study on brown bears (Ursus arctos) in the Cantabrian Mountains, Gregório et al. (2020) interpreted the asymmetrical gene flow they found from the eastern subpopulation towards the western one as an exodus of bears forced to flee from the eastern nucleus "with higher human disturbance and poaching", concluding that connectivity may be operating as a means for eastern Cantabrian bears to find more suitable territories. In this reply, we maintain that the explanations of Gregorio et al. contradict the source-sink theory and we also present demographic data not considered by these authors showing that the eastern subpopulation is not declining, but persistently increasing. After reviewing the demographic and genetic studies published during the last 20 years, we conclude that the connectivity between the two subpopulations is operating as a route which allows the regular movement of males and the restoration of the gene flow across the whole Cantabrian population.

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The efficacy of ethylene-vinyl alcohol copolymer films (EVOH) incorporating the essential oil components cinnamaldehyde (CINHO), citral (CIT), isoeugenol (IEG), or linalool (LIN) to control growth rate (GR) and production of T-2 and HT-2 toxins by Fusarium sporotrichioides cultured on oat grains under different temperature (28, 20, and 15 °C) and water activity (aw) (0.99 and 0.96) regimes was assayed. GR in controls/treatments usually increased with increasing temperature, regardless of aw, but no significant differences concerning aw were found. Toxin production decreased with increasing temperature. The effectiveness of films to control fungal GR and toxin production was as follows: EVOH-CIT > EVOH-CINHO > EVOH-IEG > EVOH-LIN. With few exceptions, effective doses of EVOH-CIT, EVOH-CINHO, and EVOH-IEG films to reduce/inhibit GR by 50%, 90%, and 100% (ED50, ED90, and ED100) ranged from 515 to 3330 µg/culture in Petri dish (25 g oat grains) depending on film type, aw, and temperature. ED90 and ED100 of EVOH-LIN were >3330 µg/fungal culture. The potential of several machine learning (ML) methods to predict F. sporotrichioides GR and T-2 and HT-2 toxin production under the assayed conditions was comparatively analyzed. XGBoost and random forest attained the best performance, support vector machine and neural network ranked third or fourth depending on the output, while multiple linear regression proved to be the worst.

Spain is a relevant producer of oats (Avena sativa), but to date there has been no study on the occurrence/co-occurrence of mycotoxins in oats marketed in Spain. The present study is addressed to overcome this lack of knowledge. One hundred oat kernel samples were acquired across different Spanish geographic regions during the years 2015–2019 and analyzed for mycotoxin content using an ultra-high performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) method and matrix-matched calibration. The focus was on the regulated mycotoxins although other relevant mycotoxins were considered. The percentage of incidence (levels ≥ limit of detection), mean and range (ng/g) of mycotoxins were as follows: zearalenone (66%, mean 39.1, range 28.1–153), HT-2 toxin (47%, mean 37.1, range 4.98–439), deoxynivalenol, (34%, mean 81.4, range 19.1–736), fumonisin B1 (29%, mean 157.5, range 63.2–217.4), and T-2 toxin, (24%, mean 49.9, range 12.3–321). Fumonisin B2, 3-acetyldeoxynivalenol, aflatoxins B1, B2, and G2, and ochratoxin A were also detected at low levels, but aflatoxin G1 was not. The maximum limits established by the European Commission for unprocessed oats were not exceeded, except for zearalenone (in one sample), and the sum of aflatoxins (in two samples). Mycotoxin co-occurrence at quantifiable levels in the same sample (two to five combinations) was found in 31% of samples. The most common mixtures were those of HT-2 + T-2 toxins alone or together with deoxynivalenol and/or zearalenone.

Abstract Introduction Because of the many HIV-related malignancies, the diagnosis and treatment of lymphoma in patients infected with human immunodeficiency virus are challenging. Objective Here, we review current knowledge of the pathogenesis, epidemiology, symptomatology, diagnosis, and treatment of head and neck lymphomas in HIV patients from a clinical perspective. Data Synthesis Although Hodgkin's lymphoma is not an AIDS-defining neoplasm, its prevalence is ten times higher in HIV patients than in the general population. NHL is the second most common malignancy in HIV patients, after Kaposi's sarcoma. In this group of patients, NHL is characterized by rapid progression, frequent extranodal involvement, and a poor outcome. HIV-related salivary gland disease is a benign condition that shares some features with lymphomas and is considered in their differential diagnosis. Conclusion The otolaryngologist may be the first clinician to diagnose head and neck lymphomas. The increasing survival of HIV patients implies clinical and epidemiological changes in the behavior of this disease. Early diagnosis is important to improve the prognosis and avoid the propagation of HIV infection.

Ross River virus, a mosquitoborne alphavirus, causes epidemic polyarthritis in Australia and the Pacific region. We analyzed serum cytokine, chemokine, and growth factor levels in travelers returning to Germany from Australia. Serum samples showed elevated concentrations in the acute phase of the illness and, more pronounced, in the long-lasting convalescent phase.

The feeding ecology of gray wolves has been investigated extensively worldwide. Despite previous studies on food habits of wolves in Asia and Iran, none has focused on the diet of the species in a scenario of depleted of wild prey and with recent records of attacks on humans. Here, we combined telemetry methods and scat analysis to study the diet of wolves in areas of Hamadan province, Iran, where medium to large wild prey is almost absent. Between October 2015 and March 2017, we studied the feeding behavior (by identifying feeding sites through clusters of GPS locations) of three wolves fitted with GPS collars, belonging to different wolf packs. We also collected and analyzed 110 wolf scats during the same period within the same areas. Overall, we investigated 850 clusters of GPS locations in the field, and identified 312 feeding sites. Most feeding clusters were linked to dumpsites and poultry farms around villages. We found 142 and 170 events of predatory (kill sites) and scavenging behavior, respectively. Prey composition based on kill sites was comprised of 74.6% livestock, 19.7% lagomorphs, 3.5% dogs, 1.4% red fox, and 0.7% golden jackal. Similarly, prey composition based on scavenging clusters was comprised of 79.9% livestock, 10.6% red fox, and 9.4% golden jackal. Scat analysis, however, indicated that livestock (34.3%), garbage (23.7%), poultry (16.0%), and European hare (15.4%) were the most frequent food items. We discuss the role of anthropogenic food sources in a context where agonistic wolf-human encounters occur recurrently, and suggest management guidelines regarding illegal dumping of animal carcasses and garbage dumpsites, in order to minimize wolf-human negative interactions.

[This corrects the article DOI: 10.1371/journal.pone.0139837.].

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El mosquito tigre, Aedes albopictus, se ha expandido por el arco mediterráneo español, incluyendo la Comunitat Valenciana. Tiene capacidad para transmitir al menos 22 arbovirosis, como dengue, enfermedad por virus de chikunguña y zika. Desde la Direcció General de Salut Pública, de la Conselleria de Sanitat Universal i Salut Pública, se han puesto en marcha actuaciones de vigilancia y control de la especie y de las enfermedades derivadas. Para abordar la lucha contra este vector se creó, desde Sanidad Ambiental, un grupo de trabajo multidisciplinar que incluye a técnicos de la administración autonómica y local así como a entomólogos universitarios. Posteriormente, se constituyó la Comisión Institucional, de ámbito directivo, donde se adquirieron compromisos clave y se impulsaron programas con actuaciones concretas. La Direcció General de Salut Pública, trabaja conjuntamente con el Laboratorio de Entomología y Control de Plagas de la Universitat de València, para dar cumplimiento a los objetivos fijados.

Large carnivores are often persecuted due to conflict with human activities, making their conservation in human-modified landscapes very challenging. Conflict-related scenarios are increasing worldwide, due to the expansion of human activities or to the recovery of carnivore populations. In general, brown bears Ursus arctos avoid humans and their settlements, but they may use some areas close to people or human infrastructures. Bear damages in human-modified landscapes may be related to the availability of food resources of human origin, such as beehives. However, the association of damage events with factors that may predispose bears to cause damages has rarely been investigated. We investigated bear damages to apiaries in the Cantabrian Mountains (Spain), an area with relatively high density of bears. We included spatial, temporal and environmental factors and damage prevention measures in our analyses, as factors that may influence the occurrence and intensity of damages. In 2006-2008, we located 61 apiaries, which included 435 beehives damaged in the study area (346 km2). The probability of an apiary being attacked was positively related to both the intensity of the damage suffered the year before and the distance to the nearest damaged apiary, and negatively related to the number of prevention measures employed as well as the intensity of the damage suffered by the nearest damage apiary. The intensity of damage to apiaries was positively related to the size of the apiary and to vegetation cover in the surroundings, and negatively related to the number of human settlements. Minimizing the occurrence of bear damages to apiaries seems feasible by applying and maintaining proper prevention measures, especially before an attack occurs and selecting appropriate locations for beehives (e.g. away from forest areas). This applies to areas currently occupied by bears, and to neighbouring areas where dispersing individuals may expand their range.

The aim of this study was to examine the impacts on blood lactate concentration, measured heart rate and assessment of perceived exertion during split sessions of equal relative load, as also their relationship to the specific sport practised. Nineteen regional-level athletes (nine middle and long-distance runners (cyclic group) and ten field-sport team players (acyclic group)) performed four high-intensity interval training (HIIT) sessions with work-interval durations of 10 s, 50 s, 90 s and 130 s. The sessions were carried out at their usual training sites with a separation of at least 48 hours. Blood lactate concentration was measured at rest and 3 min after the completion of each protocol. Heart rate was measured continuously during all sessions with a sampling rate of 1 s, and rating of perceived exertion (RPE) was requested at the end of the trial. The results showed an increase in blood lactate concentration, peak heart rate and rating of perceived exertion during long protocols as compared with short ones. No differences were observed in dependent variables between cyclic and acyclic groups. Significant but moderate correlations were observed between post-exercise blood lactate concentration, peak heart rate and RPE.

[This corrects the article DOI: 10.1371/journal.pone.0132546.].

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SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) and play important roles in regulating the PI3K/Akt pathway in physiology and disease. Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determined crystal structures containing the 5-phosphatase and a proximal region adopting a C2 fold. This reveals an extensive interface between the two domains, which results in significant structural changes in the phosphatase domain. Both the phosphatase and C2 domains bind phosphatidylserine lipids, which likely helps to position the active site towards its substrate. Although located distant to the active site, the C2 domain greatly enhances catalytic turnover. Employing molecular dynamics, mutagenesis and cell biology, we identify two distinct allosteric signaling pathways, emanating from hydrophobic or polar interdomain interactions, differentially affecting lipid chain or headgroup moieties of PI(3,4,5)P3. Together, this study reveals details of multilayered C2-mediated effects important for SHIP2 activity and points towards interesting new possibilities for therapeutic interventions.

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To clarify the presence of lymphocytic choriomeningitis virus (LCMV) in Spain, we examined blood and tissue specimens from 866 small mammals. LCMV RNA was detected in 3 of 694 wood mice (Apodemus sylvaticus). Phylogenetic analyses suggest that the strains constitute a new evolutionary lineage. LCMV antibodies were detected in 4 of 10 rodent species tested.

If it is accepted that the urban life has taken to us to live more on the 80 of our time in closed spaces would be worth the trouble to ask to us on the idea that is had of ideal inner atmospheres: spaces are wanted safer, cleaner, more healthful and better conditioned. Every time the coexistence with other live organisms beings is accepted of worse way, is wanted to have a free house of germs, insects and rodents, and to it efforts and money are dedicated to manifold. But often one forgets that the control of these undesirable organisms generates new sources of problems. The objective of the work is to analyze the problematic one derived from the presence of pests in urban areas, in special in indoors, their double slope: derived from its presence and associate to the adoption of measures of pest control based on the use of biocides. The adoption of measures at legislative level, the formation of the people implied in the accomplishment of the treatments, the awareness of the population and the update of the concept of pest control constitute the basic elements in the reduction of the risks derived from the use of pesticides in urban environments.La vida urbana nos lleva a pasar gran parte de nuestro tiempo en espacios cerrados por lo que cada vez más exigimos que sean más seguros, más limpios, más saludables, y se acepta de peor manera la convivencia con otros seres vivos; se quiere tener una casa libre de gérmenes, insectos y roedores, y a ello se dedican múltiples esfuerzos y dinero. Pero muchas veces se olvida que el control de estos organismos indeseables genera nuevas fuentes de problemas. El objetivo del trabajo es analizar la problemática derivada de la presencia de plagas en áreas urbanas, en especial en interiores, en su doble vertiente: la derivada de su presencia y la asociada a la adopción de medidas de control basadas en el empleo de biocidas. De dicho análisis se concluye que, además de la adopción de medidas a nivel legislativo, de la formación de las personas implicadas en la realización de los tratamientos, de la concienciación de la población, la actualización del concepto de control de plagas constituye un elemento clave en la reducción de los riesgos derivados del empleo de plaguicidas en áreas urbanas.

The conservation and management of wolves Canis lupus in the periphery of their distribution is challenging. Edges of wolf distribution are characterized by very few and intermittent occurrences of individuals, which are modulated by multiple factors affecting the overall population such as human-caused mortality, management targets and food availability. The knowledge of population dynamics in the edges becomes crucial when hunting takes place nearby the edges, which may preclude population expansion. Here, using as example the occurrence of wolves in the Beskydy Mountains (Czech-Slovak border), which are the edge distribution of the wolf and Eurasian lynx Lynx lynx populations in the West Carpathians, we explored how food availability and hunting in the Slovakian core area affected the dynamics of wolves in the edges of this population. During 2003-2012, we monitored large carnivore occurrence by snow-tracking surveys and tested potential differences in the occurrence of these species in Beskydy Mountains and potential mechanisms behind detected patterns. Despite the proximity to the core area, with several wolf reproductions being confirmed at least in recent years, the wolf was a very rare species in Beskydy and was recorded 14 times less often than the lynx. The expected abundance of wolves in the Beskydy Mountains was inversely related to prey availability in the Slovakian core area. Wolf hunting the year before influenced the expected abundance of wolves in Beskydy area. We discuss how different life histories and legal status of both species probably account for most of the observed difference of occurrence at range margins.

Friedreich's ataxia (FRDA), the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin deficiency-induced phenotypes. Taken together, these results demonstrate that the metal dysregulation in FRDA includes other metals besides iron, therefore providing a new set of potential therapeutic targets.

Population monitoring is crucial for wildlife management and conservation. In the last few decades, wildlife researchers have increasingly applied bioacoustics tools to obtain information on several essential ecological parameters, such as distribution and abundance. One such application involves wolves (Canis lupus). These canids respond to simulated howls by emitting group vocalizations known as chorus howls. These responses to simulated howls reveal the presence of wolf litters during the breeding period and are therefore often used to determine the status of wolf populations. However, the acoustic structure of chorus howls is complex and discriminating the presence of pups in a chorus is sometimes difficult, even for experienced observers. In this study, we evaluate the usefulness of analyses of the acoustic energy distribution in chorus howls to identify the presence of pups in a chorus. We analysed 110 Iberian wolf chorus howls with known pack composition and found that the acoustic energy distribution is concentrated at higher frequencies when there are pups vocalizing. We built predictive models using acoustic energy distribution features to determine the presence of pups in a chorus, concluding that the acoustic energy distribution in chorus howls can be used to determine the presence of wolf pups in a pack. The method we outline here is objective, accurate, easily implemented, and independent of the observer's experience. These advantages are especially relevant in the case of broad scale surveys or when many observers are involved. Furthermore, the analysis of the acoustic energy distribution can be implemented for monitoring other social canids that emit chorus howls such as jackals or coyotes, provides an easy way to obtain information on ecological parameters such as reproductive success, and could be useful to study other group vocalizations.