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Los macroútiles han sido habitualmente marginados de los estudios, debido al peso que ha tenido la industria lítica tallada para la observación de los cambios y continuidades cronológicos y culturales. Sin embargo, estos elementos aparecen en yacimientos arqueológicos asociados a diferentes contextos geográficos y cronológicos, lo cual les confiere un valor como marcadores de la adaptación y de la evolución técnica desarrollada por los grupos humanos. En este trabajo se presentan los resultados del análisis detallado de un objeto procedente del yacimiento de Hort de Cortés-Volcán del Faro (València), asociado a niveles gravetienses. La singularidad de su morfología, de la materia prima y la presencia de huellas de uso apreciables a nivel macroscópico motivaron la aplicación de diferentes metodologías de estudio sobre la pieza para su comprensión. El análisis de las huellas de uso apunta a que esta roca carbonatada fue utilizada en actividades asociadas con el tratamiento de la piel. La diferenciación de dos grupos de huellas de uso ha determinado la distinción de dos tareas desarrolladas con el objeto. La presencia de residuos que se pueden correlacionar con el uso de la pieza se ha evaluado aplicando una aproximación multianalítica y no destructiva. Además, se han aplicado técnicas de espectroscopía atómica y molecular junto con estadística multivariante, con el objetivo de identificar la potencial fuente de materia prima. El interés de este estudio reside en la combinación de aproximaciones para el estudio de un macroútil. Todo ello ha permitido ampliar la limitada información que se tiene sobre este tipo de materiales, y abrir el debate sobre el conocimiento del nivel tecnológico alcanzado por los grupos humanos.

Background: Previous studies have shown that meal timing, poor sleep quality, and chronotype may play a relevant role in the development of type 2 diabetes mellitus (T2DM). However, its relationship with macronutrients by eating occasions has not been explored deeply. Objective: Our aim was to estimate the association between chrono-nutrition, sleep quality, chronotype, and the prevalence of T2DM. Methods: This cross-sectional study included a subset of 3465 middle-aged Caucasian adults (2068 women) from the European Prospective Investigation into Cancer and Nutrition (EPIC) Spain cohort study. In the 2017–18 follow-up, we assessed chronotype, sleep quality, diet, and sociodemographic data using validated questionnaires. Further, we used blood samples to determine serum levels of glucose. We defined a case of T2DM when serum glucose concentration was ≥126 mg/dL or when participants self-reported diabetes. Results: A higher prevalence of T2DM was associated with poor sleep quality (ORpoorvsgood = 2.90, 95% CI = 1.30, 6.28). Carbohydrate intake at breakfast was inversely associated with the prevalence of T2DM (OR = 0.75, 95% CI = 0.66, 0.85). Finally, lipid intake at breakfast was associated with a 13% higher prevalence of T2DM (OR = 1.13, 95% CI = 1.01, 1.26) for each 1 standard deviation (1-SD) increase. Conclusions: This study concludes that a higher content of carbohydrates at breakfast is correlated with a reduced prevalence of T2DM, while higher lipids intake at breakfast is associated with a higher prevalence of T2DM. Furthermore, poor sleep quality is a potential factor associated with an elevated prevalence of T2DM. Our results emphasize the need for prospective studies to validate and strengthen these observed associations.

Abstract Leaves are colonized by a complex mix of microbes, termed the leaf microbiota. Even though the leaf microbiota is increasingly recognized as an integral part of plant life and health, our understanding of its interactions with the plant host is still limited. Here, mature, axenically grown Arabidopsis thaliana plants were spray inoculated with six diverse leaf‐colonizing bacteria. The transcriptomic changes in leaves were tracked over time and significant changes in ethylene marker (ARL2) expression were observed only 2–4 days after spray inoculation. Whole‐transcriptome sequencing revealed that 4 days after inoculation, leaf transcriptional changes to colonization by nonpathogenic and pathogenic bacteria differed in strength but not in the type of response. Inoculation of plants with different densities of the nonpathogenic bacterium Williamsia sp. Leaf354 showed that high bacterial titers resulted in disease phenotypes and led to severe transcriptional reprogramming with a strong focus on plant defense. An in silico epigenetic analysis of the data was congruent with the transcriptomic analysis. These findings suggest (1) that plant responses are not rapid after spray inoculation, (2) that plant responses only differ in strength, and (3) that plants respond to high titers of nonpathogenic bacteria with pathogen‐like responses.

Natural deep eutectic solvents (NADES) have emerged as an eco-friendly alternative for extracting bioactives, avoiding the use of flammable organic solvents and extreme temperatures and pH conditions. NADES rely on intermolecular interactions between hydrogen bonding donors (HBD) and hydrogen bonding acceptors (HBA) to form eutectic mixtures with significantly lower melting points than their individual components. These matrices are influenced by factors like water content, temperature, and component ratios. NADES high viscosity can hinder extractive efficiency, which can be mitigated by adding water or working at higher temperatures. However, excessive dilution with water may disrupt the supramolecular structure of NADES, reducing extraction efficiency. A notable feature of NADES is their fine-tunability for specific purposes. Adjusting physicochemical properties such as polarity, pH, and viscosity optimizes extraction efficiency by promoting the solubility of target molecules and interactions between the NADES and target molecules. NADES, unlike organic solvents, can partially disrupt plant and microalgae cell walls, enhancing permeability and extraction efficiency. Moreover, NADES can have a stabilising effect on bioactives and can enhance their biological activity and bioavailability. These attributes, coupled with their low environmental impact in terms of low toxicity and high biodegradability, make NADES attractive for biorefinery applications.

The objective of this work was to prepare different concentrations of liposomes based on lecithin containing quercetin, and evaluate their effect on the properties of galactomannan films obtained from Cassia grandis seeds. Quercetin-loaded lecithin liposomes (QT-LL) were obtained by the ethanol injection method by incorporating quercetin in different concentrations in a previously prepared suspension of lecithin liposomes in water. Following characterization of QT-LLs by zeta potential and dynamic light scattering, QT-LL with 75 µg quercetin/mL suspension was incorporated at different concentrations in galactomannan films. The films obtained were characterized for color, solubility, moisture content (MC), water vapor permeability (WVP), scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectroscopy. The size of lecithin liposomes with no quercetin was statistically than those containing quercetin above 50 µg/mL. All the QT-LLs presented a low polydispersity index, even considering their significant differences and similar values for zeta potential. The films displayed a rough surface and the galactomannan structure was confirmed by FTIR. Additionally, the amorphous nature of the polysaccharide was observed by XRD. The films were luminous, with a predominant yellow tendency and low opacity. The incorporation of QT-LL in galactomannan films did not lead to statistical differences for solubility and MC, while significant differences were observed for WVP. Galactomannan films were shown to be a promising structure for the incorporation of lecithin liposomes loaded with quercetin, pointing at promising applications for different applications.

This study was conducted between March 2020 and February 2021 to analyze anxiety and depression symptoms in 64 women with gestational trophoblastic disease (GTD) and 99 women who had miscarried. The Hospital Anxiety and Depression Scale (HADS) was applied by telephone three months after pregnancy loss. Multivariate analysis was performed using hierarchical logistic regression to evaluate associations between variables. Probable anxiety (HADS-A ≥ 8) and depression (HADS-D ≥ 8) were found in 53.1% and 43.8% of the GTD group and 49.5% and 39.4% of the miscarriage group, with no difference between the groups. Severe symptoms of anxiety (HADS-A 15-21) and depression (HADS-D 15-21) were found, respectively, in 12.5% and 4.7% of the GTD group and in 9.1% and 4.0% of the miscarriage group, also with no difference between the groups. Lack of partner support proved a risk factor for anxiety and depression, while poor education increased the risk of depression symptoms 3.43-fold following pregnancy loss. In conclusion, three months after pregnancy loss the frequency of anxiety and depression symptoms was similarly high in both groups, with poor education and lack of partner support being significant risk factors for the subsequent development of psychiatric morbidity.

Abstract Objective To investigate the prevalence of histopathological subtypes, the clinical stage at presentation and treatment modalities in Polish patients with orbital lymphoma (OL) and to determine prognostic outcomes. Methods The retrospective study of 107 patients with OL treated in a 14‐year period in Polish hematological centers. The analysis included histopathological subtype, disease clinical advancement, treatment modalities, progression‐free survival (PFS), and overall survival (OS). Results The median patient age was 60 years (range 51–71). Mucosa‐associated lymphoid tissue (MALT) lymphoma accounted for slightly more than half of all cases of orbital lymphoma (51%). The second most common subtype was diffuse large B‐cell lymphoma (DLBCL) (29%). Primary orbital lymphoma was diagnosed in 48% of all patients. According to the Ann Arbor, localized stage IE of orbital lymphoma was diagnosed only in 39% of all patients. Systemic involvement was observed in more than half of all patients (52%). The median follow‐up period was 30 months (range 0–160 months). Patients with non‐MALT lymphoma had a significantly inferior PFS compared to patients with MALT lymphoma, (p = 0.047). Patients with primary orbital lymphoma had a superior PFS compared to patients with secondary orbital lymphoma [median PFS 104.5 months vs. 33.4 months], (p = 0.069). Younger patients with MALT lymphoma were characterized by superior PFS (median PFS not reached) compared to other studied subgroups of patients (older patients with MALT lymphoma, younger and older non‐MALT lymphoma patients) with a median PFS of 30.5, 32.2, 32.6 months respectively (p = 0.039). Patients treated with chemotherapy alone had inferior PFS compared to patients treated with combined therapies (p = 0.034). The median PFS across patients who received chemotherapy alone was 23.7 months, whereas across other patients was 73.9 months. Conclusions Secondary lymphoma accounts for more than half of the orbital lymphoma in Polish population. The advanced clinical stage of the disease (non‐IE according to Ann Arbor) concerns two‐thirds of the overall population of patients with orbital lymphomas and one‐third of MALT lymphoma patients. The high incidence of advanced stages of orbital lymphoma may indicate the need for combined treatment. Combined orbital lymphoma treatment is associated with superior PFS compared to chemotherapy alone in overall population of patients with orbital lymphoma.

Background: The consumption of processed meats (PMs) and red meats are linked to the likelihood of developing colorectal cancer. Various theories have been proposed to explain this connection, focusing on nitrosyl-heme and heme iron intake. We hypothesized that differences in nitrosyl-heme and heme iron intakes will be associated with various sociodemographic and lifestyle factors. Methods: The study included 38,471 healthy volunteers (62% females) from five Spanish regions within the EPIC-Spain cohort. High-Performance Liquid Chromatography (HPLC) determined nitrosyl-heme and heme iron levels in the 39 most consumed PMs. Food intake was assessed using validated questionnaires in interviews. Nitrosyl-heme and heme iron intakes, adjusted for sex, age, body mass index (BMI), center, and energy intake, were expressed as geometric means due to their skewed distribution. Variance analysis identified foods explaining the variability of nitrosyl-heme and heme iron intakes. Results: The estimated intakes were 528.6 µg/day for nitrosyl-heme and 1676.2 µg/day for heme iron. Significant differences in nitrosyl-heme intake were found by sex, center, energy, and education level. Heme iron intake varied significantly by sex, center, energy, and smoking status. “Jamón serrano” and “jamón cocido/jamón de York” had the highest intake values, while “morcilla asturiana” and “sangrecilla” were key sources of nitrosyl-heme and heme iron. Conclusions: This is the first study to estimate levels of nitrosyl-heme intake directly in PMs for a large sample, revealing variations based on sex, BMI, smoking, and activity. Its data aids future exposure estimations in diverse populations.

ABSTRACT Objectives: to assess the relationship between spiritual well-being, symptoms and performance of patients under palliative care. Methods: this is a descriptive correlational study, conducted with 135 patients seen in palliative care outpatient clinics. Karnofsky Performance Status Scale, Edmonton Symptom Assessment Scale, Spirituality Scale and Hospital Anxiety and Depression Scale were used. Data were submitted to descriptive statistical analysis and Spearman’s correlation. Results: among participants, 68.2% were cancer patients. The most prevalent symptoms were changes in well-being (65.2%), anxiety (63.7%), sadness (63%) and fatigue (63%). Sadness, dyspnea, sleepiness, anxiety and depression presented weak to moderate correlation with spiritual well-being. Symptom overload showed weak negative correlation with performance. Conclusions: symptom intensification was correlated with worsening in spiritual well-being perception. The reduction in performance was related to increased number of symptoms, especially depression and anxiety.

Background and aims: Alexithymia and psychological symptomatology have been closely associated with gambling disorder (GD). However, sex differences remain underexplored. This study aims, firstly, to explore the differences between groups (GD and no-GD) and sexes (women vs. men) in alexithymia and psychological symptomatology (depression, anxiety and hostility). Secondly, the relationship between alexithymia and psychological symptomatology was analysed by gambling and sex groups. Thirdly, it examines the moderation role of sex and gambling in the relationship between alexithymia and each psychological symptom. Method: The sample was composed of 80 people with GD diagnosis and 80 without GD (40 women and 40 men in each group). Results: The results showed that alexithymia is positively related to depression, anxiety and hostility, with significantly higher scores in people with GD. Moderation analyses showed a threefold interaction, in which higher alexithymia was related to higher depression for men with GD but not for GD-women. However, in women with GD, depression levels are higher than in people without GD and tend to be more stable over time, despite the lack of effect of alexithymia. Conclusions: These results provide evidence indicating that dysfunctional psychological symptomatology affects people with GD to a greater extent than people without GD, but also that the aetiology and effect of underlying vulnerability factors on gambling is different according to sex. The need of prevention and treatment programmes that consider different psychological aspects depending on sex is reinforced.

IntroductionEating disorders (EDs) and behavioural addictions show common psychological vulnerability factors such as alexithymia and stressful life events (SLE). This study aims, firstly, to explore the prevalence and latent profiles of participants based on their risk of suffering EDs, gambling disorder (GD), alcohol and/or drug abuse, and compulsive buying (CB) by sex. Secondly, it aimed to test whether alexithymia and having experienced SLE are associated with group membership.MethodsThe sample was predominantly drawn from university students and social networks. It was composed of 352 young adults between 18 and 35 years old, of whom 77.8% were women and 22.2% men.ResultsThe results showed that the most prevalent disorders of the sample were alcohol, EDs, CB, drugs and GD, respectively. Moreover, latent class analyses were conducted based on the risk of suffering EDs or addictions by sex. Three main profiles were found: ‘Men with addictions’, ‘Healthy women’ and ‘Women with EDs’. Finally, differences in SLE and alexithymia levels were tested by latent classes. “Men with addictions” and “Women with EDs” had higher scores on alexithymia and SLE than the group of “Healthy women”. However, the group of “Women with EDs” (class 3) reported significantly higher levels of SLE and alexithymia than the other two groups.Discussion and conclusionIn conclusion, we discuss the possibility that some vulnerability factors operate generally and transdiagnostically in EDs and addictive disorders. The identification of clinical phenotypes could complement and deepen prediction, prevention and treatment research in clinical settings. The need to take sex and gender differences into account is reinforced.

We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of non-thyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone (TH) level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients from 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2–63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; stan dardized mean difference (SMD) 1.16; 95% CI, 0.41–1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31–0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in thyrotropin levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (odds ratio (OR) = 2.21, 95% CI, 1.64–2.97, I2 = 65% P < 0.01). The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.

Conventional extraction techniques are usually based on highly pollutant and/or flammable organic solvents. Therefore, alternative environmentally friendly extraction methods are of particular interest for the recovery of bioactive compounds for their application as food ingredients and/or nutraceuticals. Natural deep eutectic solvents (NADES) are a green and nontoxic attractive alternative to hydroalcoholic extraction. NADES media primarily depends on the intermolecular interactions (hydrogen bonding) among their components to form a eutectic mixture with a much lower final melting point than its individual components. Examples of natural deep eutectic NADES solvents include aqueous solutions (25%–50% water) of choline chloride, sugars, and polyols. This study aimed to investigate the application of two NADES, namely, betaine:triethylene glycol (Bet : TEG) and choline chloride:1,2-propanediol (Chol : Prop), as sustainable green solvents for the extraction of polyphenols from spent coffee ground (SCG), a by-product of coffee processing. In particular, the extraction yield and selectivity were evaluated and compared with conventional green extractions (hot water and a hydroalcoholic solution). In addition, the effect of NADES on the antioxidant and antimicrobial activity of the extracts was investigated. The main outcomes were as follows: (i) NADES were as effective as other conventional green solvents in the extraction of polyphenols with the added advantage of operating at milder temperature conditions, without flammable solvents and with sustainable and natural compounds; (ii) the antimicrobial activity of the NADES extracts was 10 times higher than that of the ethanolic and aqueous extracts. Given the low toxicity of NADES, they could be used as formulation aid for food ingredients.

Abstract Background Falls are a common and serious health issue facing the global population, causing an estimated 646,000 deaths per year globally. Wearable devices typically combine accelerometers, gyroscopes and even barometers; using the data collected and inputting this into an algorithm that decides whether a fall has occurred. The purpose of this umbrella review was to provide a comprehensive overview of the systematic reviews on the effectiveness of wearable electronic devices for falls detection in adults. Methods MEDLINE, Embase, Cochrane Database of Systematic Reviews (CDSR), and CINAHL, were searched from their inceptions until April 2019 for systematic reviews that assessed the accuracy of wearable technology in the detection of falls. Results Seven systematic reviews were included in this review. Due to heterogeneity between the included systematic reviews in their methods and their reporting of results, a meta-analysis could not be performed. Most devices tested used accelerometers, often in combination with gyroscopes. Three systematic reviews reported an average sensitivity of 93.1% or greater and an average specificity of 86.4% or greater for the detection of falls. Placing sensors on the trunk, foot or leg appears to provide the highest accuracy for falls detection, with multiple sensors increasing the accuracy, specificity, and sensitivity of these devices. Conclusions This review demonstrated that wearable device technology offers a low-cost and accurate way to effectively detect falls and summon for help. There are significant differences in the effectiveness of these devices depending on the type of device and its placement. Further high-quality research is needed to confirm the accuracy of these devices in frail older people in real-world settings.

BackgroundEpidemiological studies have demonstrated an association between the degree of food processing in our diet and the risk of various chronic diseases. Much of this evidence is based on the international Nova classification system, which classifies food into four groups based on the type of processing: (1) Unprocessed and minimally processed foods, (2) Processed culinary ingredients, (3) Processed foods, and (4) “Ultra-processed” foods (UPF). The ability of the Nova classification to accurately characterise the degree of food processing across consumption patterns in various European populations has not been investigated so far. Therefore, we applied the Nova coding to data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in order to characterize the degree of food processing in our diet across European populations with diverse cultural and socio-economic backgrounds and to validate this Nova classification through comparison with objective biomarker measurements.MethodsAfter grouping foods in the EPIC dataset according to the Nova classification, a total of 476,768 participants in the EPIC cohort (71.5% women; mean age 51 [standard deviation (SD) 9.93]; median age 52 [percentile (p)25–p75: 58–66] years) were included in the cross-sectional analysis that characterised consumption patterns based on the Nova classification. The consumption of food products classified as different Nova categories were compared to relevant circulating biomarkers denoting food processing, measured in various subsamples (N between 417 and 9,460) within the EPIC cohort via (partial) correlation analyses (unadjusted and adjusted by sex, age, BMI and country). These biomarkers included an industrial transfatty acid (ITFA) isomer (elaidic acid; exogenous fatty acid generated during oil hydrogenation and heating) and urinary 4-methyl syringol sulfate (an indicator for the consumption of smoked food and a component of liquid smoke used in UPF).ResultsContributions of UPF intake to the overall diet in % grams/day varied across countries from 7% (France) to 23% (Norway) and their contributions to overall % energy intake from 16% (Spain and Italy) to >45% (in the UK and Norway). Differences were also found between sociodemographic groups; participants in the highest fourth of UPF consumption tended to be younger, taller, less educated, current smokers, more physically active, have a higher reported intake of energy and lower reported intake of alcohol. The UPF pattern as defined based on the Nova classification (group 4;% kcal/day) was positively associated with blood levels of industrial elaidic acid (r = 0.54) and 4-methyl syringol sulfate (r = 0.43). Associations for the other 3 Nova groups with these food processing biomarkers were either inverse or non-significant (e.g., for unprocessed and minimally processed foods these correlations were –0.07 and –0.37 for elaidic acid and 4-methyl syringol sulfate, respectively).ConclusionThese results, based on a large pan-European cohort, demonstrate sociodemographic and geographical differences in the consumption of UPF. Furthermore, these results suggest that the Nova classification can accurately capture consumption of UPF, reflected by stronger correlations with circulating levels of industrial elaidic acid and a syringol metabolite compared to diets high in minimally processed foods.

Heavy menstrual bleeding (HMB) is profuse, acyclic bleeding from the genital tract, with or without clots, usually lasting more than 10 days. They are the most common cause of abnormal uterine bleeding in adolescence. The following are used in the treatment: iron preparations, antifibrinolytic drugs, NSAIDs, estrogen-progestagen therapy or progestagen therapy. In cases where the Hb concentration is

Abstract Background Hemophilia carriers experience abnormal bleeding symptoms; however, a lack of awareness about this topic coupled with additional knowledge gaps and barriers leads to suboptimal care for this population. Objective The primary objective was to describe the current knowledge gaps and challenges from the perspective of both hemophilia carriers and their health care providers. Methods We carried out a mixed methods descriptive study with two population groups between September and December 2020. The hemophilia carrier perspective was obtained through both focus groups and questionnaires, whereas the health care providers perspective obtained via questionnaire sent to the Association of Hemophilia Care Directors of Canada and the Canadian Association of Nurses in Hemophilia Care. Focus groups were analyzed using descriptive thematic analysis and quantitative survey data was also analyzed. Results Eleven hemophilia carriers participated along with 19 health care providers (11 physicians, eight nurses). Hemophilia carrier focus group discussions identified four areas representing major challenges or knowledge gaps: (1) negative psychosocial impacts; (2) difficulty determining symptom significance; (3) need for self‐advocacy; (4) testing concerns. Survey results from both groups were aligned with the most important topics for ongoing education identified as information on abnormal bleeding symptoms, where to seek treatment, and considerations for heavy menstrual bleeding/menstruation. The majority of both study groups believe obligate or potential carriers should have factor levels checked regardless of age if symptoms of abnormal bleeding occur or before an invasive procedure. However, hemophilia carriers were significantly more in favor of genetic testing under the age of consent than health care providers in all scenarios evaluated.

Novel hybrid core-shell structures, in which up-converting (UC) NaYF4:Yb,Tm core converts near-infrared (NIR) to visible (Vis) light via multiphoton up-conversion processes, while anatase TiO2-acetylacetonate (TiO2-Acac) shell ensures absorption of the Vis light through direct injection of excited electrons from the highest-occupied-molecular-orbital (HOMO) of Acac into the TiO2 conduction band (CB), were successfully synthesized by a two-step wet chemical route. Synthesized NaYF4:Yb,Tm@TiO2-Acac powders were characterized by X-ray powder diffraction, thermogravimetric analysis, scanning and transmission electron microscopy, diffuse-reflectance spectroscopy, Fourier transform infrared spectroscopy, and photoluminescence emission measurement. Tetracycline, as a model drug, was used to investigate the photocatalytic efficiencies of the core-shell structures under irradiation of reduced power Vis and NIR spectra. It was shown that the removal of tetracycline is accompanied by the formation of intermediates, which formed immediately after bringing the drug into contact with the novel hybrid core-shell structures. As a result, ~80% of tetracycline is removed from the solution after 6 h.

BackgroundColorectal cancer (CRC) is a heterogeneous disease with variable mutational profile and tumour microenvironment composition that influence tumour progression and response to treatment. While chemoresistant and poorly immunogenic CRC remains a challenge, the development of new strategies guided by biomarkers could help stratify and treat patients. Allogeneic NK cell transfer emerges as an alternative against chemoresistant and poorly immunogenic CRC.MethodsNK cell-related immunological markers were analysed by transcriptomics and immunohistochemistry in human CRC samples and correlated with tumour progression and overall survival. The anti-tumour ability of expanded allogeneic NK cells using a protocol combining cytokines and feeder cells was analysed in vitro and in vivo and correlated with CRC mutational status and the expression of ligands for immune checkpoint (IC) receptors regulating NK cell activity.ResultsHLA-I downmodulation and NK cell infiltration correlated with better overall survival in patients with a low-stage (II) microsatellite instability-high (MSI-H) CRC, suggesting a role of HLA-I as a prognosis biomarker and a potential benefit of NK cell immunotherapy. Activated allogeneic NK cells were able to eliminate CRC cultures without PD-1 and TIM-3 restriction but were affected by HLA-I expression. In vivo experiments confirmed the efficacy of the therapy against both HLA+ and HLA− CRC cell lines. Concomitant administration of pembrolizumab failed to improve tumour control.ConclusionsOur results reveal an immunological profile of CRC tumours in which immunogenicity (MSI-H) and immune evasion mechanisms (HLA downmodulation) favour NK cell immunosurveillance at early disease stages. Accordingly, we have shown that allogeneic NK cell therapy can target tumours expressing mutations conferring poor prognosis regardless of the expression of T cell-related inhibitory IC ligands. Overall, this study provides a rationale for a new potential basis for CRC stratification and NK cell-based therapy.

Abstract Objectives To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days. Trial design Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial Participants The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Participants are recruited from hospital sites in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and the United States of America. The inclusion criteria are: 1) Laboratory confirmed COVID-19 (diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification) prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission; 2) Admitted to hospital for COVID-19; 3) One D-dimer value above the upper limit of normal (ULN) (within 5 days (i.e. 120 hours) of hospital admission) AND EITHER: a. D-Dimer ≥2 times ULN OR b. D-Dimer above ULN and Oxygen saturation ≤ 93% on room air; 4) > 18 years of age; 5) Informed consent from the patient (or legally authorized substitute decision maker). The exclusion criteria are: 1) pregnancy; 2) hemoglobin 1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 6) patient already prescribed intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration); 7) patient already prescribed therapeutic anticoagulation at the time of screening [low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban)]; 8) patient prescribed dual antiplatelet therapy, when one of the agents cannot be stopped safely; 9) known bleeding within the last 30 days requiring emergency room presentation or hospitalization; 10) known history of a bleeding disorder of an inherited or active acquired bleeding disorder; 11) known history of heparin-induced thrombocytopenia; 12) known allergy to UFH or LMWH; 13) admitted to the intensive care unit at the time of screening; 14) treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening; 15) Imminent death according to the judgement of the most responsible physician; 16) enrollment in another clinical trial of antithrombotic therapy involving hospitalized patients. Intervention and comparator Intervention: Therapeutic dose of LMWH (dalteparin, enoxaparin, tinzaparin) or high dose nomogram of UFH. The choice of LMWH versus UFH will be at the clinician’s discretion and dependent on local institutional supply. Comparator: Standard care [thromboprophylactic doses of LMWH (dalteparin, enoxaparin, tinzaparin, fondaparinux)] or UFH. Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is generally considered standard care. Main outcomes The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Secondary outcomes include (evaluated up to day 28): 1. All-cause death 2. Composite of ICU admission or all-cause death 3. Composite of mechanical ventilation or all-cause death 4. Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation; 5. Red blood cell transfusion (>1 unit); 6. Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; 7. Renal replacement therapy; 8. Hospital-free days alive; 9. ICU-free days alive; 10. Ventilator-free days alive; 11. Organ support-free days alive; 12. Venous thromboembolism (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 13. Arterial thromboembolism (defined as suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 14. Heparin induced thrombocytopenia; 15. Trajectories of COVID-19 disease-related coagulation and inflammatory biomarkers. Randomisation Randomisation will be stratified by site and age (>65 versus ≤65 years) using a 1:1 computer-generated random allocation sequence with variable block sizes. Randomization will occur within the first 5 days (i.e. 120 hours) of participant hospital admission. However, it is recommended that randomization occurs as early as possible after hospital admission. Central randomization using an interactive web response system will ensure allocation concealment. Blinding (masking) No blinding involved. This is an open-label trial. Numbers to be randomised (sample size) 462 patients (231 per group) are needed to detect a 15% risk difference, from 50% in the control group to 35% in the experimental group, with power of 90% at a two-sided alpha of 0.05. Trial Status Protocol Version Number 1.4. Recruitment began on May 11th, 2020. Recruitment is expected to be completed March 2022. Recruitment is ongoing. Trial registration ClinicalTrials.gov Identifier: NCT04362085 Date of Trial Registration: April 24, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Rose Selwyn (1824–1905) was a first wave Australian feminist and public speaker. The poetry, art, and scraps of writing Rose left in her archive allow the reader to piece together an intellectual history, a genealogy of the making of self. Rose attained her way of being through several contemporary influences—the mysticism of Tractarianism, a concern with death and its meanings, an interest in the literary edges of the world, a concern with the suffering body, and a passion for women and a woman-centred world. From these tangled contemporary concerns, she made a feminism for all non-Aboriginal women apparent in her speeches. Her role as a colonising woman in a violent landscape created a complex relationship with Aboriginal people where she may be seen to be criticising her elite landholding (squatter) peers and introducing concepts such as an Aboriginal parliament.

Since the classification of processed meat as carcinogenic by the International Agency for Research on Cancer (IARC) in 2015, an increase in consumption of plant-based meat alternatives (PBMAs) has been observed worldwide. This occurs in a context characterized by concern for health, animal welfare, and sustainability; however, evidence of their nutritional quality is still limited. Therefore, our objective was to evaluate the nutritional profile and processing degree of PBMAs available in Spain. In 2020, products from seven Spanish supermarkets were analyzed for their nutritional content and ingredients. Of the 148 products, the majority were low in sugars but moderate in carbohydrates, total and saturated fat, and high in salt. The main vegetable protein sources were soy (91/148) and wheat gluten (42/148). Comparatively, 43/148 contained animal protein, the most common being egg. Overall, PBMAs had a long list of ingredients and additives, and they were classified as ultra-processed foods (UPFs) according to the NOVA system. This study shows that the PBMAs available in Spanish supermarkets have a variable nutritional composition within and between categories. Further research is needed to determine if replacing meat with these UPFs could be a good alternative towards healthier and more sustainable dietary patterns.

This study explores the potential benefits of spices (cinnamon and ginger) on Roselle anthocyanins within a sweetened Roselle beverage matrix. Anthocyanins and other related properties of the beverage (colour, antioxidant capacity, total phenolics, and pH) were observed from the start and monitored for 30 days at accelerated storage conditions (40 °C). The sweeteners at the amounts used (80 g/L granulated sugar and 0.32 g/L Stevia Reb A) did not have a significant effect on the initial anthocyanin content in the beverage and did not significantly impact degradation. Upon the addition of spices to the sweetened beverage, ginger (1 g/L) did not result in significant changes, initially or during storage. However, following the addition of cinnamon (1 g/L) to the beverages (unsweetened and sweetened), an initial increase in the total phenolic and FRAP antioxidant activity in the Roselle beverages was observed; furthermore, it reduced the degradation of anthocyanins and improved colour stability during storage. This effect is postulated to be due to a co-pigmentation reaction or the acylation of anthocyanins with a complex formed from the reaction of glucose with the phenolic compounds contained in cinnamon.

Abstract Background The Canadian Bleeding Disorders Registry (CBDR) captures data from 24 hemophilia treatment centers and patients directly. Nonacog beta pegol (N9‐GP) was approved in Canada in 2018. Objectives To assess treatment outcomes following switching to N9‐GP in a real‐world setting. Methods CBDR data for Canadian male patients (aged 7–72 years) with hemophilia B receiving prophylactic N9‐GP for ≥6 months as of March 31, 2021, were included. To allow comparison with the previously used products, only patients for whom data were available in the CBDR for at least 6 months before the switch to N9‐GP were included in this retrospective analysis. Results Forty‐two patients were included in the analysis (total observation period: 148.0 patient‐years). The distribution of disease severity was 62% severe, 36% moderate, 2% mild, with 62% of patients previously receiving recombinant factor IX‐Fc‐fusion protein (rFIXFc) and 38% previously receiving standard half‐life (SHL) recombinant factor IX (rFIX). During a median follow‐up period of 2.3 years on N9‐GP prophylaxis, 232 bleeds were reported in 30 patients, 29% of patients reported zero bleeds. The median overall annualized bleeding rate on N9‐GP was 0.73 for patients switching from rFIXFc (previously 1.44) and 2.10 for patients switching from SHL rFIX (previously 6.06). Median total annualized factor consumption (IU/kg) was lower with N9‐GP than with previous SHL rFIX (2152 vs 3018) and previous rFIXFc (1766 vs 2278). Conclusions Results from this first real‐world study of N9‐GP in patients with hemophilia B suggest optimal bleeding control with low factor consumption after switching to N9‐GP, irrespective of the previous product.

This study reports on efforts over several years to design and implement a yearlong intervention intended to support secondary mathematics teachers in their early years of teaching. The intervention is designed to retain early career mathematics teachers in the professions by engaging them in the development of meaningful professional relationships with a school-based mentors, and by creating an online community of practice for support with other professionals. The intervention itself consists of early career teachers and their mentors participating in monthly professional learning activities such as online meetings, videoconferencing panels with experts, and collaborative reading and discussing timely, purposeful, and relevant content. The intervention is designed to not over burden the participants and to be feasible for national implementation with little to no funding. This article presents the purpose, design, and implementations of the intervention, as well as a discussion of challenges faced and potential next steps and future directions for similar work.

IntroductionLipid disorders are the most important risk factor of cardiovascular disease (CVD). For clinical practice and assessment of patient`s cardiovascular risk the most relevant is to determine plasma concentration of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Blue-collar workers are a group of patients with higher estimated cardiovascular risk than other workers groups.The aim of the studyThe aim of the study was to asses prevalence of lipid disorders in blue-collar workers from Lubelskie region.Material and methodsThe method of this paper was to perform a retrospective analysis of data provided by the National Health Fund. The study population enclosed patients aged 35, 40, 45, 50, 55 included in the Cardiovascular Disease Prevention Program held in Primary Healthcare (PH) setting on the area of Lubelskie region in years 2008-2018. Patients analyzed were blue-collar workers. The chi-square test was used to test the relationship between the two qualitative features and the Pearson linear correlation between the quantitative features. The analyzes were performed using the IBM SPSS Statistics for Windows, version 25 program (IBM Corp., Armonk, N.Y., USA). The significance level was assumed to be α = 0,05.ResultsIn 26 226 patients hyperlipidemia was observed in 65,6% and LDL cholesterol levels higher than 115 mg/dl in 52,8% of patients. The mean total cholesterol serum concentration was 203,8 mg/dl, LDL cholesterol - 120,1 mg/dl and median triglycerides concentration – 101,0 mg/dl.ConclusionsHyperlipidemia was a common problem in blue-collar workers in Lubelskie region in years 2008-2018. Intense prophylactic actions are needed to reduce cardiovascular risk of this group of population.

IntoductionAccidents and injuries are a major challenge for modern medicine. According to EUROSTAT data from 2016, accidents were the fifth most frequent cause of death among citizens of the European Union countries. Injuries of the urogenital-tract represent about 10% of all injuries, thanks to epidemiological analysis it is possible to continuously improve the effects of their treatment.AimThe aim of this study is to analyze the epidemiology of urogenital-tract injuries in 2006-2018 in Poland, in the region of Lublin Voivodeship, and to compare them with other papers on a similar subject.Material and methodsThe retrospective analysis was carried out on all patients with S-T diagnosis according to ICD-9 treated in hospitals in the Lublin Voivodeship in 2006-2018. The analysis was based on statistical data collected by the National Institute of Public Health – National Institute of Hygiene. There were 934 patients selected. The collected material was analyzed statistically using the STATISTICA 13.1 program.ResultsOut of 934 patients the vast majority were men (n=782, 83.73%), the remaining part of analyzed population was women (n=152, 16.27%). The average age of the analyzed group was 33 years 5 months, injuries were most common in 15-30 years old group. Mortality of urogenital-tract injuries in the analyzed group was 0.75%. The most frequent injuries were to the external genitals (55.4%) followed by renal (29.66%) and urethra (5.56%) bladder (3.43%). Urinary injuries were very rare.ConlusionsInjuries to the urogenital-tract most often involve young men. They are relatively rare and their mortality rate is low. External genital trauma is the most common injury to the urogenital-tract, while renal injury is the most common within the urinary tract. Occasionally injuries to other organs of the urinary tract occur. The main mechanism of injury is blunt but within the lower urinary tract a significant role is played by iatrogenic injuries.

Abstract Background Patients with type 1 von Willebrand disease (VWD) undergo a desmopressin (DDAVP) responsiveness challenge at diagnosis to assess whether DDAVP reverses their coagulation deficits. Current practice assumes DDAVP responsiveness remains constant over the lifetime. In patients with type 1 VWD, VWF‐related parameters increase with age. This study explores whether DDAVP responsiveness also differs with age in this population. Methods We conducted a retrospective chart review of 106 patients enrolled at our center since 1990. Our primary outcome was DDAVP responsiveness at 1 hour after DDAVP challenge. Locally weighted scatterplot smoothing fit and Spearman correlation coefficients were used to study the relationship between age and DDAVP responsiveness. For female participants, we used the Kruskal‐Wallis test to compare absolute and relative changes in DDAVP responsiveness at various ages. Results We had 79 patients (56 female) with type 1 VWD with at least 1 DDAVP challenge. In women with type 1 VWD, the absolute change in DDAVP responsiveness did not vary significantly with age (VWF:antigen [Ag], −0.08, P = .56; VWF:ristocetin cofactor [RCo], −0.16, P = .26; low‐molecular‐weight component of factor VIII [FVIII:C], −0.01, P = .93), nor did the relative change in DDAVP responsiveness (VWF:Ag, −0.03, P = .86; VWF:RCo, −0.25, P = .09; FVIII:C, −0.14, P = .34). The data plot suggested a relationship. Conclusion In women with type 1 VWD, DDAVP responsiveness may vary over the life cycle. Our exploratory findings are limited by our retrospective data, cross‐sectional design, and small sample. Future studies should investigate the relationship between age and DDAVP responsiveness prospectively to evaluate whether there is clinical utility in rechallenging postpubertal female patients with type 1 VWD.

Midwifery training in Krakow started within the University structures and was closely related to the reform of the Academy in 1780. Following H. Kołłątaj and Prof. A. Badurski’s ideas, the first clinical hospital was created in Krakow, where midwifery training started. Prof. R. Czer-wiakowski gave lectures for midwives and supervised the maternity clinic. The changing political relations remodelled the structure and organisation of the school authorities, which affected the working conditions of the University. Obtaining a diploma was preceded by the so-called strict exam in front of an exam board consisting of professors. The positive result of the exam then authorised the student to take an oath in front of the Dean, the secretary, and a professor of the Faculty of Medicine, which, as stated on the diploma, gave “the right to prac-tice midwifery”. Following professors and heads of the maternity clinic made special efforts in organising midwifery courses and improving continuously difficult learning conditions. Many documents issued to midwives or provided by midwifery students have survived from their professional activity. Prof. H. Jordan achieved outstanding results in this respect, as he managed to obtain permission from the partitioning authorities to organise an independent midwifery school. It opened in 1895, and Prof. A. Mars became its head. The importance of achieving this idea promoted by Prof. H. Jordan for the further development of midwives in Krakow is worth emphasising. The independent institution took the name of the Imperial Royal School of Midwives.

Background: The RECOURSE trial supported trifluridine/tipiracil as a treatment option in metastatic colorectal cancer (mCRC). Subsequent analysis demonstrated that low tumour burden and indolent disease are good prognosis factors improving progression-free survival (PFS) and overall survival (OS). This study aimed to evaluate the impact of prognosis group in the OS, PFS and safety of trifluridine/tipiracil in patients with mCRC. Methods: Single-centre, retrospective, and observational study of patients with mCRC who started trifluridine/tipiracil between February 2018 and July 2019. Patients were divided into good prognosis characteristics (GPC) [low tumour burden (less than 3 metastasis site) and indolent disease (≥18 months from first metastasis diagnosis)] and poor prognostic characteristics (PPC) group [high tumour burden (3 or more metastasis sites) and/or aggressive disease (

Background: Recent evidence suggest that energy distribution during the daytimecould be a potential determinant for the development of metabolic syndrome (MetS). Objective: To cross-sectionally assess the association between breakfast size and the prevalence of MetS in Spanish adults. Methods: Our study included a subset of 3644 participants from the European Prospective Investigation into Cancer and Nutrition Spain study recontacted between 2017–2018. Information on diet, sociodemographic, lifestyle, sleep quality, and chronotype was collected using standardized questionnaires, while anthropometric and blood pressure data were measured in a face-to-face personal interview by a nurse. MetS was defined according to the Adult Treatment Panel III (ATPIII) definition by measuring serum levels of total cholesterol, tryglycerides and glucose. Breakfast size was calculated as: (energy from breakfast/total energy intake) * 2000 kcal. To evaluate the association between breakfast size and MetS prevalence, a multivariable logistic regression model adjusted by potential confounders was used to estimate OR and 95% CI. Results: Prevalence of MetS in our study was 40.7%. The mean breakfast size was 306.6 * 2000 kcal (15% of the total daily energy intake), with 14 (0.4%) participants skipping breakfast. Participants in the highest quartile of breakfast size had a lower MetS prevalence compared to participants in the lowest quartile (ORQ4vsQ1 = 0.62; 95% CI = 0.51–0.76; p-trend < 0.001). No modification of the estimated ORs by sex, breakfast time, and number of eating occasions per day were observed. Conclusion: Our results suggest that higher breakfast size is associated with lower prevalence of MetS in Spanish adults, supporting the importance of a high energy breakfast. Further prospective studies are necessary to confirm these findings.

Patients on hemodialysis show dysregulated immunity, basal hyperinflammation and a marked vulnerability to COVID-19. We evaluated the immune profile in COVID-19 hemodialysis patients and the changes associated with clinical deterioration after the hemodialysis session. Recruited patients included eight hemodialysis subjects with active, PCR-confirmed SARS-CoV-2 infection, five uninfected hemodialysis patients and five healthy controls. In SARS-CoV-2-infected hemodialysis patients TNF-α, IL-6 and IL-8 were particularly increased. Lymphopenia was mostly due to reduction in CD4+ T, B and central memory CD8+ T cells. There was a predominance of classical and intermediate monocytes with reduced HLA-DR expression and enhanced production of pro-inflammatory molecules. Immune parameters were analysed pre- and post-hemodialysis in three patients with COVID-19 symptoms worsening after the hemodialysis session. There was a higher than 2.5-fold increase in GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-17A and IL-21 in serum, and augmentation of monocytes-derived TNF-α, IL-1β and IL-8 and CXCL10 (p < 0.05). In conclusion, COVID-19 in hemodialysis patients associates with alteration of lymphocyte subsets, increasing of pro-inflammatory cytokines and monocyte activation. The observed worsening during the hemodialysis session in some patients was accompanied by augmentation of particular inflammatory cytokines, which might suggest biomarkers and therapeutic targets to prevent or mitigate the hemodialysis-related deterioration during SARS-CoV-2 infection.

The need for a comprehensive, high-quality pipeline for the development of undergraduate pre-service teachers, especially those that represent a diverse student body, within STEM disciplines is acute. Here, we studied the NoyceSCIENCE program to determine the most impactful experiences offered to undergraduates through the lens of student development theory. We used qualitative coding to analyze data collected from journals (n = 29) written by students of varying backgrounds, and at varying levels within the program (i.e., the Scholar and Intern level) over a 3-year program running period. We observed that faculty mentorship, the ability of undergraduates to mentor others, volunteer experiences, and learning directly from experts had the greatest influence on student development overall. For Scholars that participate for more than 1 year in the program, access to undergraduate mentoring and volunteering experiences contributed most to student development. We posit that these findings are broadly applicable to other science learning communities and STEM content-focused teacher preparation programs as they are program components that can be integrated in isolation or in their entirety.

BackgroundFood biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population.Methods and findingsWe examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual's yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10-P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out.ConclusionsIn this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines.

Background: The term phyllodes tumours, which account for less than 1% of breast neoplasms, describes a spectrum of heterogenous tumours with different clinical behaviours. Less than 30% present as metastatic disease. Complete surgical resection is the standard of care so that recurrence rates are reduced. The role of adjuvant chemotherapy or radiation therapy is controversial. Patients with metastatic disease have a median overall survival of around 30 months. Case description: The authors present the case of a 57-year-old woman with an exuberant left malignant phyllodes tumour with bilateral involvement, as well as lung and axillar metastasis. The patient underwent haemostatic radiation therapy and started palliative chemotherapy with doxorubicin, achieving partial response with significant improvement in quality of life. A posterior simple mastectomy revealed a small residual tumour. Discussion: Metastatic malignant phyllodes tumours are rare, so therapeutic strategies rely on small retrospective studies and guidelines for soft tissue sarcoma. Palliative chemotherapy protocols include anthracycline-based regimens, either as monotherapy with doxorubicin or doxorubicin together with ifosfamide. With few treatment options, management of these patients must rely on a continuum of care

Una óptima selección deportiva está formada por la valoración del genotipo (dermatoglifía) y el fenotipo (somatotipo, composición corporal y capacidades físicas). El propósito del estudio fue determinar la relación entre la dermatoglifía y el perfil morfo-funcional en deportistas profesionales de futbol sala en la ciudad de Bogotá. La muestra estuvo conformada por 12 hombres, quienes fueron evaluados antropométricamente, con porcentaje graso de 18,4 ± 5,9; masa músculo-esquelética de 32,4 ± 4,4 kg y un somatotipo endo-mesomórfico. Por medio de la dermatoglifía se determinó predominancia en los diseños dactilares presilla (69,2±23,1), D10 (11,3±3,6), SQTL (140,7±95,1). Por último, se valoró la fuerza explosiva con la prueba de Squat Jump, en la cual la posición de poste logró mayor altura. En conclusión, existe una predisposición hacia las capacidades físicas de velocidad, potencia, coordinación y resistencia, además la fuerza explosiva es mayor en deportistas con menor valor en el componente endomórfico y en el porcentaje de masa grasa.

Male germ cells experience a drastic chromatin remodeling through the nucleo-histone to nucleo-protamine (NH-NP) transition necessary for proper sperm functionality. Post-translational modifications (PTMs) of H4 Lys5, such as acetylation (H4K5ac), play a crucial role in epigenetic control of nucleosome disassembly facilitating protamine incorporation into paternal DNA. It has been shown that butyrylation on the same residue (H4K5bu) participates in temporal regulation of NH-NP transition in mice, delaying the bromodomain testis specific protein (BRDT)-dependent nucleosome disassembly and potentially marking retained nucleosomes. However, no information was available so far on this modification in human sperm. Here, we report a dual behavior of H4K5bu and H4K5ac in human normal spermatogenesis, suggesting a specific role of H4K5bu during spermatid elongation, coexisting with H4K5ac although with different starting points. This pattern is stable under different testicular pathologies, suggesting a highly conserved function of these modifications. Despite a drastic decrease of both PTMs in condensed spermatids, they are retained in ejaculated sperm, with 30% of non-colocalizing nucleosome clusters, which could reflect differential paternal genome retention. Whereas no apparent effect of these PTMs was observed associated with sperm quality, their presence in mature sperm could entail a potential role in the zygote.

Abstract Abnormal or excessive menstrual bleeding affects one‐third of reproductive‐aged women. This number increases to 70% among women on direct oral anticoagulants (DOACs). While there is some variation in frequency of heavy menstrual bleeding (HMB) with different DOAC options, all menstruating individuals should receive counseling about the risk of HMB at the time of DOAC initiation. Management options include progestin‐only therapies such as the levonorgestrel intrauterine system and etonogestrel subdermal implant or the progestin‐only pill. Combined hormonal contraceptives and depot medroxyprogesterone acetate are associated with increased rates of thrombosis in nonanticoagulated women but may be continued, or even initiated, so long as therapeutic anticoagulation is ongoing. Procedural therapies, such as endometrial ablation, uterine artery embolization, or hysterectomy, are considerations for women who have completed childbearing and for whom more conservative measures are objectionable or ineffective. Given the high rates of HMB in women on DOACs, management strategies should be discussed even before heavy bleeding is diagnosed, particularly in women who experienced HMB prior to DOAC initiation. As iron deficiency with or without anemia is a common complication of HMB, complete blood count and ferritin levels should be monitored periodically, and iron deficiency should be treated with oral or intravenous iron supplementation.

Introduction: Appendicitis can be classified as non-perforated and perforated; based on such classification, the reported organ-space surgical site infection (OS-SSI) rate is 0.8% and 18%, respectively. Objective: To establish the prevalence of OS-SSI in patients with perforated appendicitis treated in a pediatric hospital in 2012. Materials and methods: Retrospective, observational and descriptive study conducted at Fundación Hospital Pediátrico La Misericordia, with a random sample of 200 patients, of which 160 met the inclusion criteria. Results: 20 patients (12.5%) presented with OS-SSI and all of them received antibiotic treatment; 70% did not require abscess drainage. Patients ≥8 years of age had 5 times more abscesses than younger ones (17.6% vs. 3.4%). OS-SSI was found in 33% of patients with free fecalith and in 50% of the patients who required postoperative management at the ICU vs. 9.5% of the patients who received management in the intermediate care unit and the inpatient hospital floors. The total rate of surgical site infection was 24.3% (11.8% superficial, 0% deep and 12.5% organ-space). Conclusions: The prevalence of OS-SSI found here is lower than what has been reported in the literature. Being 8 years or older and having free fecalith are risk factors to develop this type of infection. The higher frequency of OS-SSI in patients treated at the ICU during the post-operative period observed here suggests that this condition may be associated with septic shock.

Introduction According to the current state of knowledge, breastfeeding is the best method of feeding newborns, infants and young children. World organizations and associations and authorities of the medical world recommend breast milk as the most suitable for the proper development of the child. Natural feeding brings many important health benefits, both for the mother and the child, and promotes the formation of emotional ties. It is also economical and convenient to use. The purpose of the studywas to assess the attitudes of women towards breastfeeding and the state of their knowledge on the subject. Material and methods The study group consisted of 96 mothers of children treated in the Department of Neonate and Infant Pathology at the University Children's Hospital in Lublin. The study used the method of a diagnostic survey using a questionnaire constructed by the authors. The obtained results were analyzed using the STATISTICA 12.5 program. Results 53.9% of respondents gave a positive answer to the question about breastfeeding their own child. As the main reasons for its interruption were given most often too little food (36.6%) and child's illness (26.8%). 79.8% of women replied that the help of health care workers in breastfeeding training is needed, but only 56.2% of respondents believe that the information obtained was sufficient. Only 41.6% of respondents knew that lactation affects fertility and the possibility of becoming pregnant. In the question whether breastfeeding allows a better relationship between the mother and the child, 95.5% gave a positive answer. 98.9% emphasized the positive impact of breastfeeding on the relationship between parents. As many as 60.7% of women intended to give up natural feeding after returning to work. Conclusions A surprisingly high percentage of women resign from natural feeding, despite relatively good knowledge about the benefits resulting from it. Advice from healthcare professionals is an important source of information for women. Breastfeeding after returning to work is an important problem.

Introduction A brain tumor is the most common solid cancer in children and the most common cause of cancer-related death in this age group. Its first symptom presented by child may be some irritation symptoms, primarily in the form of focal seizures. In case of such problem clinician has a wide range of neuroimaging methods available. Case Report A 16-year-old girl was admitted to the Paediatric Department on December 6, 2018 after the first episode of generalized tonic-clonic seizures with retrograde amnesia. In EEG paroxysmal acute and slow theta-delta 3-4 Hz high-voltage discharge in the temporal leads and in CT with contrast no focal changes. The treatment was postponed due to fact that was the first episode of seizures in life, On June 4, 2019 a second epileptic attack occurred. CT of the head without contrast did not reveal focal changes. In EEG focal lesion in the right posterior temporo-occipital-parietal region in the form of low-voltage slow delta 1-2 Hz waves and concomitant seizure changes in the form of very numerous short discharges of acute and slow theta-delta 3-4 Hz waves. In MRI, in the occipital lobe cortex at the height of the wedge and the visual cortex after administration of the gadolinium contrast agent 3 focal lesions with contrast augmentation: 7mm and below 2 changes 15x6mm in diameter and 5mm in diameter were visualized. In the flair and T2 sequence at this height there was edema of up to 25x13mm. Conclusions CT of the head without contrast should be a screening test to exclude mainly traumatic changes and intracranial bleeding. The correct picture of such an examination does not exclude abnormalities within the brain structures. MRI is more accurate in imaging of brain structures and should be the examination of choice if CNS diagnostics is needed.

Introduction Trauma is defined as damage to cells, tissues and organs caused by external factors acting on them. According to WHO data, trauma caused 4.8 millions of deaths in 2016. Urogenital trauma occurs in 10% of all the injuries in the human population. Aim of the study The aim of this study was to characterize the patients treated for injuries in Urology Department in Regional Hospital in Poland and compare the results with the data from literature. Material and methods The study involved patients hospitalized in Regional Specialist Hospital in Puławy, Poland from 2007 to 2018. The survey was based at analysis of medical documentation. The collected data has been subjected to statistical analysis. 66 patients were included in the study group. Their average age was 43.25 years. Results The absolute majority of patients were men – 81.81% (n=54), women – 18.18% (n=12). The average age for males was 42.27 and for the females – 44.25. Most frequent trauma in our study was the renal trauma 36.36% (n=24). 47.06% of this injuries were associated with MVA's. The second most frequent group was a genital trauma - 21 patients (31,81%). 81.81 % of them required surgical treatment. Another group constituted 10.6 % (n=7) were the patients treated for bladder injury. Penis was injured in 6.06% (n=4), 75% of patients required a surgery. Urether has been injured only in 4.55%. Conclusions Kidney is the most frequent organ of genitourinary tract, affected by trauma, particularly during MVA's. Victims are usually treated conservatively. External genitalia injuries, especially male, are also very frequent. Mostly patients need a rapid surgical intervention but appropriate treatment allows the patient to recover completely without any lasting disability

Introduction: Family Medicine is a relatively new specialisation in Poland, that was created to increase availability of comprehensive medical care near the place of residence. Due to the major deficiency of human resources there is a huge need of educating medical personnel. Objectives: This study is an evaluation of knowledge level and attitudes towards family medicine specialisation of The Lublin Medical University Medical Faculty 5th year students, starting their family medicine classes. Results: Among the respondents 1.49% declared willingness to start family medicine specialisation, 40.89% is considering this career path, 39.03% is not considering this career path, 18.59% is definitely not considering this specialisation. Main factors, which are the reasons why students consider undertaking family medicine specialisationwere: flexible working hours (79.82%), wide range of patient’s ailments (78.07%), no on-call time (73.68%). On the other hand, students consider job in PHC as monotonous and hardly prestigious and 94.1% of respondents assessed that cooperation of family physicians with other specialisations is average at best. Only 13% correctly indicated what are the factors the amount of money per patient depends on. Majority of students correctly named family physicians’ responsibilities and medical examinations that family physician can perform under the agreement with National Health Fund. Conclusion: Research gathered in this document indicate on little interest in family medicine specialisation among students and at the same time on lack of certain knowledge about job in PHC. Thus, there is a need to create relevant educational programmes which would turn future doctor’s attention to general practice.

Previous research has demonstrated that working memory performance is linked to mathematics achievement. Most previous studies have involved children and arithmetic rather than more advanced forms of mathematics. This study compared the performance of groups of adult mathematics and humanities students. Experiment 1 employed verbal and visuo-spatial working memory span tasks using a novel face-matching processing element. Results showed that mathematics students had greater working memory capacity in the visuo-spatial domain only. Experiment 2 replicated this and demonstrated that neither visuo-spatial short-term memory nor endogenous spatial attention explained the visuo-spatial working memory differences. Experiment 3 used working memory span tasks with more traditional verbal or visuo-spatial processing elements to explore the effect of processing type. In this study mathematics students showed superior visuo-spatial working memory capacity only when the processing involved had a comparatively low level of central executive involvement. Both visuo-spatial working memory capacity and general visuo-spatial skills predicted mathematics achievement.

Introduction Infection is the most common cause of children medical consultations. Often the clinical picture of the patient is disproportionate to the results of laboratory tests which may indicate for generalized infection. Case reports Case 1: A 4-year-old patient admitted to the Department due to a fever 39˚C lasting from 2 days and periodic abdominal pain. Good general condition, throat slightly red. In laboratory studies, procalcitonin 44.5 ng/ml, CRP 121.5 mg/dl, WBC 15.32 ths/ul. Empirical treatment with ceftriaxone and vancomycin was included. Blood cultures, Staphylococcus hominis MLSB, MRCNS. Case 2: A patient nearly 5 years old admitted to the Department due to a fever 39.5˚C. In outpatient examinations CRP 41 mg/dl, WBC 39 ths/ul. Physical examination: reddening of throat mucosa, palatine tonsils slightly enlarged, reddish, without rash. In laboratory tests CRP 95 mg/dl, WBC 41.95 ths/ul, PCT 1.19 ng/ml. On the second day of hospitalization, an increase in inflammatory markers was observed (PCT 1.47 ng/ml, CRP 235.7 mg/dl). Vancomycin was added. Case3: 18-month-old boy admitted to the Department due to fever 40.5˚C. Good general condition, throat slightly reddened, occasional cough. In laboratory tests PCT 8.07 ng/ml. Empirical antibiotic therapy with ceftriaxone was implemented. Due to persistence of fever up to 39.5˚C - control tests of PCT 10.03 ng / ml. Vancomycin was implemented. Urine culture negative, in blood culture the present growth of Staphylococcus warneri. Conclusions It is extremely important to be vigilant in case of feverish children. Sometimes, despite a good general condition and no significant abnormalities in a physical examination, we can deal with generalized infection.