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Manuel F Bande Rodríguez, 1, 2 Beatriz Fernandez Marta, 1 Nerea Lago Baameiro, 3 Maria Santiago-Varela, 1, 2 Paula Silva-Rodríguez, 2, 4 María Jose Blanco-Teijeiro, 1, 2 Maria Pardo Perez, 3 Antonio Piñeiro Ces 1, 2 1Unidad de Retina Quirúrgica y Tumores Intraoculares del Adulto (URQTIA), Servicio de Oftalmología Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Santiago de Compostela, Spain; 2Tumores Intraoculares en el Adulto, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; 3Grupo Obesidómica, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; 4Fundación Pública Galega de Medicina Xenómica, Clinical University Hospital, SERGAS, Santiago de Compostela 15705, SpainCorrespondence: Manuel F Bande RodríguezUnidad de Retina Quirúrgica y Tumores Intraoculares del Adulto (URQTIA), Servicio de Oftalmología Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Santiago de Compostela, SpainTel +34981951756Fax +34981956189Email verman017@hotmail.comAbstract: The detection of metastases in patients with a diagnosis of uveal melanoma (UM) is a controversial issue. While only 1% of the patients have detectable metastases at the time of diagnosis, up to 30% of them will develop liver metastases within 5 years of treatment. UM spreads hematogenously, therefore, blood biomarkers may be helpful for prognosis and monitoring the disease progression. Despite the great progress achieved thanks to the genetic analysis of UM biopsies, this is an invasive technique and is limited by the heterogeneity of the tumor. The present review considers the current understanding in the field regarding biomarkers for the diagnosis and prognosis of UM and its metastasis, primarily to the liver. General covered topics include non-conventional markers such as proteins previously identified in cutaneous melanoma and UM cell lines, circulating tumor cells, microRNAs (miRNA), and circulating DNA, and how each may be critical in the development of novel blood biomarkers for UM.Keywords: uveal melanoma, biomarker, circulating tumor cells, microRNAs, circulating DNA, exosome

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Purpose: This case-control study investigated whether defects in visual field contrast sensitivity are associated with exposure to occupational levels of pesticides in agricultural workers., Methods: Twenty-seven individuals exposed to occupational levels of pesticides (exposed group) from 14 agricultural systems and 27 non-exposed individuals (non-exposed group) were measured using standard automated perimetry (30-2 full threshold). Visual sector analysis, targeting regions of the optic nerve head, was performed to examine for potential region-specific sensitivity differences. Participants also underwent comprehensive assessments, including general optometric examinations and demographic surveys. Symptoms and signs of neurotoxicity were assessed using the modified Q16 neurotoxic symptom questionnaire and biological testing for abnormal levels of Substance P in tears (an inflammatory marker associated with chemical exposure) and cholinesterase (which is inhibited by pesticides) in blood samples., Results: Signs of chemical exposure were found as indicated by significantly higher levels of neurotoxic symptoms, higher concentrations of Substance P and lower levels of cholinesterase in the exposed group. Visual field global indices showed differences in contrast sensitivity between the exposed and non-exposed groups, with the exposed group demonstrating significantly lower means and larger pattern-standard deviations. Notably, visual field sector analysis revealed comparatively lower contrast sensitivity at nasal locations surrounding the optic nerve head in the exposed group., Conclusion: This study found deficits in visual field contrast sensitivity to be associated with pesticide exposure, and selective loss at nasal locations centred on the optic nerve head may indicate retinal toxicity. These findings suggest the utility of visual field assessment as a potential method to evaluate pesticide-related health implications. The results highlight the need for ongoing monitoring and protective measures for agricultural workers exposed to pesticides to prevent potential visual and neurological damage., (© 2024 College of Optometrists.)

Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are the main interventional treatments for coronary artery disease (CAD) patients. Both procedures are constantly being perfected and developed. This study aims to analyze the evolution of intervention mortality rates of PCI and CABG in recent years in Spain. We use a database of all hospital discharges from CABG and PCI procedures in Spain during two periods, between the years 2010 to 2012 and 2016 to 2019. We elaborate two multivariate regression logistic models to test the differences in mortality between the two periods and the two procedures, adjusting the mortality rates by age, gender, and comorbidities. We find strong evidence that CABG significantly reduced mortality rates, especially in complex patients, while PCI remained almost constant. We also discuss how physicians incorporate the improvement in procedures' performance into the decision-making for the recommendation of these two procedures in CAD patient management.

Background and Importance: Complete posterior atlantoaxial dislocation (PAAD) with an unfractured odontoid process is a rare condition where a dislocated but intact odontoid process is positioned ventrally to the anterior arch of C1. This lesion is related to transverse and alar ligament rupture secondary to hyperextension and rotatory traumatic injury and is often associated with neurological deficit. The treatment strategy remains controversial, and in many cases, odontoidectomy is required. Traditional approaches for odontoidectomy (transnasal and transoral) are technically demanding and are related to several complications. This article describes a 360° reduction and stabilization technique through a navigated anterior full-endoscopic transcervical approach (nAFETA) as a novel technique for odontoidectomy and C1-C2 anterior transarticular fixation supplemented with posterior fusion., Clinical Presentation: A 21-year-old man presented to the emergency room by ambulance after a motorcycle accident. On evaluation, incomplete ASIA B spinal cord injury was documented. Imaging revealed a complete PAAD. We performed a two-staged procedure, a nAFETA odontoidectomy plus C1-C2 anterior transarticular fixation followed by posterior C1-C2 wired fusion. At a 2-year follow-up, the patient had a 10-point Oswestry Disability Index score and neurological improvement to ASIA E., Conclusion: PAAD can be successfully treated through minimally invasive nAFETA. Noteworthy, the risks of the transoral and endonasal routes were avoided through this approach. In addition, nAFETA allows anterior transarticular fixation during the same procedure providing spinal stability. Further studies are required to expand the use of nAFETA in this field., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: Violence against children (VAC) is a global public health and human rights issue that can lead to long-lasting negative consequences for individual and societal outcomes. While extensive evidence indicates that parenting programmes might be effective in preventing VAC, there are several unsolved questions on how to ensure interventions are acceptable, feasible, effective and sustainable, particularly in low- and- middle-income countries (LMICs)., Method: In this study, we report findings from a qualitative examination of policymakers' (N = 10), early childhood and parenting programme facilitators' (N = 20) and parents' and other caregivers' (N = 38) perspectives on VAC prevention to examine the implementation ecosystem of parenting programmes in Colombia, including contextual risk and protection factors, features of existing programmes, and stakeholders' needs. We conducted interviews and focus groups using a semistructured format, along with a thematic approach, to analyse the data from each group of participants (i.e., policymakers, facilitators and caregivers) independently., Results: Overall, the data revealed the critical role of intersecting and interacting factors at the micro (e.g., caregivers' capabilities and beliefs), meso (e.g., programme content and delivery approaches) and macro (e.g., policymakers' vision and existing infrastructure) levels in exacerbating risks/imposing barriers versus protecting/promoting VAC prevention., Conclusions: These findings provide evidence on the implementation ecosystem of prevention programmes to inform the design of novel strategies and programmes aimed at preventing violence and promoting families' well-being and young children's development., (© 2024 John Wiley & Sons Ltd.)

Stroke is the leading cause of disability and the second cause of death worldwide. The increasing burden of stroke underscores the importance of optimising rehabilitation protocols. Virtual reality (VR) can improve poststroke prognosis. A VR software combining gamification, full immersion and stroke specificity (ie, the Development and validation of a novel viRtual rEality software for improving diSability and quality of lifE in patients with sTroke (RESET) software) might substantially improve disability and quality of life (QoL). However, this technology is still very scarce. The RESET trial aims to assess the effects of an early 10-week gamified, fully immersive and stroke-specific VR intervention (ie, starting at week 3 poststroke) on disability and QoL in people with stroke in the subacute phase. People with ischaemic or haemorrhagic stroke (n=94) aged ≥ 18 years will be randomised to receive (1) usual care (UC), (2) commercial VR or (3) gamified, fully immersive and stroke-specific VR ( RESET ). The three groups will receive UC (ie, three sessions/week of 90 min of standard rehabilitation). The VR groups will additionally receive three VR sessions of 20 min per week. The outcome measures will be assessed at baseline (week 2 from stroke occurrence), week 13 (approximately 90 days from the event) and week 26 (approximately 6 months from the event). The primary outcome is disability measured with the Barthel Index. Secondary outcomes include QoL, upper-extremity and lower-extremity motor function, gross manual dexterity, handgrip strength and cognitive function. This study will unravel the effects of a gamified, fully immersive and stroke-specific VR software on disability and QoL in patients with stroke in the early subacute phase.Trial registration number: NCT06132399., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study provides a comprehensive overview of hereditary hemochromatosis (HH), a genetic condition characterized by iron overload due to excessive iron absorption. It elucidates diverse inheritance patterns and clinical manifestations by exploring mutations in critical genes such as HFE (hemochromatosis), HJV (hemojuvelin), HAMP (hepcidin antimicrobial peptide), TfR2 (transferrin receptor 2), and FP (ferroportin). The significance of early screening, diagnosis, and personalized management strategies based on genetic classification is emphasized, particularly in terms of high-income vs. low-income countries. Addressing challenges in diagnosis, genetic testing accessibility, and healthcare disparities, the study highlights the importance of early detection, cost-effective screening strategies, and enhancing healthcare outcomes globally. Advanced genetic testing in high-income countries facilitates early diagnosis and management, reducing complications such as liver disease and cardiomyopathy. In contrast, low-income populations face several barriers, including limited access to genetic testing, high costs, and inadequate healthcare infrastructure. Cost-effective serum ferritin (SF) and transferrin saturation (TS) tests and emerging point-of-care (POC) tests offer affordable diagnostic options for low-resource settings. Additionally, the ongoing development of hepcidin measurement methods holds promise for enhancing diagnostic capabilities. Implementing these strategies can aid healthcare providers in improving global HH management and reducing the burden of iron overload complications. Furthermore, the study underscores the need for public health initiatives to raise awareness about HH, promote routine screenings, and advocate for equitable healthcare policies. Collaborative efforts between governments, healthcare organizations, and research institutions are crucial in addressing the global burden of HH. By fostering international cooperation and resource-sharing, it is possible to bridge the gap between high-income and low-income countries, ensuring all individuals have access to the necessary diagnostic and treatment options. This holistic approach can ultimately lead to better health outcomes and improved quality of life for individuals affected by HH worldwide. This comprehensive examination of HH not only illuminates the genetic and clinical aspects of the condition but also provides a roadmap for addressing the multifaceted challenges associated with its diagnosis and management., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Villa Nogueyra et al.)

Purpose: Uveal melanoma is the most prevalent intraocular malignancy in adults, derived from uveal tract melanocytes. This study focuses on the frequency and risk of second primary malignancies in UM patients., Methods: A PubMed search (1980-2023) identified studies on SPM incidence in UM patients. From 191 references, 14 studies were chosen, focusing on UM, SPMs, and analysing data on demographics and types of neoplasms., Results: Among 31,235 UM patients in 14 studies, 4695 had 4730 SPMs (15.03% prevalence). Prostate (15%), breast (12%), and colorectal (9%) cancers were most common. Digestive system malignancies were highest (19%), with colorectal cancer leading (51%). Breast and prostate cancers were prevalent in respective systems. Lung, bladder, and non-Hodgkin's lymphoma were also notable. The study observed an increasing trend in the frequency of SPMs over time, reflecting broader trends in cancer survivorship and the growing prevalence of multiple malignancies., Conclusion: The study highlights a significant presence of SPMs in UM patients, with an increasing trend in frequency over time, emphasizing prostate and breast cancers. This underscores the need for focused surveillance and tailored follow-up for UM survivors, considering their higher risk of additional malignancies. Future research should further investigate SPM aetiology in UM patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Melatonin (ML) and dexmedetomidine (DM) are used separately as anesthetic premedication or as an anesthetic in humans and laboratory animals. In this study, we aimed to investigate the anesthetic properties of both drugs combined. The anesthetic effects of several combinations of ML (50 and 100 mg/kg) and DM (50 and 100 μg/kg) were evaluated in rats by observing behavioral manifestations and recording the duration and depth of anesthesia. Five anesthetic intervals were established according to the loss and recovery of reflexes. While each individual drug did not induce an appropriate anesthetic effect at the tested doses, ML50 + DM100, ML100 + DM50 and ML100 + DM100 combinations resulted in surgical anesthesia intervals of 60 to 360 min. Together, our results point that the use of ML allows to decrease the dose of DM, reducing the unwanted anesthetic effects of this α 2 -agonist., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide, one person dies by suicide every 40 s, making it a major health problem. Studies in families have suggested that suicide has a genetic component, so the search for genetic variants associated with suicidal behavior could be useful as potential biomarkers to identify people at risk of suicide. In Mexico, some studies of gene variants related to neurotransmission and other important pathways have been carried out and potential association of variants located in the following genes has been suggested: SLC6A4 , SAT-1 , TPH-2 , ANKK1 , GSHR , SCARA50 , RGS10 , STK33 , COMT , and FKBP5. This systematic review shows the genetic studies conducted on the Mexican population. This article contributes by compiling the existing information on genetic variants and genes associated with suicidal behavior, in the future could be used as potential biomarkers to identify people at risk of suicide.

Staphylococcus aureus is one of the most prevalent pathogens causing bovine mastitis in the world, in part because of its ease of adaptation to various hosts and the environment. This study aimed to determine the prevalence of S. aureus in Colombian dairy farms and its relationship with the causal network of subclinical mastitis. From thirteen dairy farms enrolled, 1288 quarter milk samples (QMS) and 330 teat samples were taken from cows with positive (70.1%) and negative California Mastitis Test (CMT). In addition, 126 samples from the milking parlor environment and 40 from workers (nasal) were collected. On each dairy farm, a survey was conducted, and the milking process was monitored on the day of sampling. S. aureus was identified in 176 samples, i.e., 138 QMS, 20 from teats, 8 from the milking parlor environment, and 10 from workers' nasal swabs. Isolates identified as S. aureus underwent proteomics (clustering of mass spectrum) and molecular (tuf, coa, spa Ig, clfA, and eno genes) analysis. Regarding proteomics results, isolates were distributed into three clusters, each with members from all sources and all farms. Concerning molecular analysis, the virulence-related genes clfA and eno were identified in 41.3% and 37.8% of S. aureus isolates, respectively. We provide evidence on the circulation of S. aureus strains with limited variability among animals, humans, and the environment. The parameters with the lowest compliance in the farms which may be implicated in the transmission of S. aureus are the lack of handwashing and abnormal milk handling., (© 2023. The Author(s).)

Staphylococcus is a very prevalent etiologic agent of bovine mastitis, and antibiotic resistance contributes to the successful colonization and dissemination of these bacteria in different environments and hosts on dairy farms. This study aimed to identify the antimicrobial resistance (AMR) genotypes and phenotypes of Staphylococcus spp. isolates from different sources on dairy farms and their relationship with the use of antibiotics. An antimicrobial susceptibility test was performed on 349 Staphylococcus strains ( S. aureus , n = 152; non-aureus staphylococci (NAS), n = 197) isolated from quarter milk samples (QMSs) from cows with subclinical mastitis (176), the teats of cows (116), the milking parlor environment (32), and the nasal cavities of milk workers (25). Resistance and multidrug resistance percentages found for S. aureus and NAS were ( S. aureus = 63.2%, NAS = 55.8%) and ( S. aureus = 4.6%, NAS = 11.7%), respectively. S. aureus and NAS isolates showed resistance mainly to penicillin (10 IU) (54.1% and 32.4%) and ampicillin (10 mg) (50.3% and 27.0%) drugs. The prevalence of AMR Staphylococcus was higher in environmental samples (81.3%) compared to other sources (52.6-76.0%). In S. aureus isolates, the identification of the blaZ (83.9%), aacAaphD (48.6%), ermC (23.5%), tetK (12.9%), and mecA (12.1%) genes did not entirely agree with the AMR phenotype. We conclude that the use of β-lactam antibiotics influences the expression of AMR in Staphylococcus circulating on dairy farms and that S. aureus isolates from the environment and humans may be reservoirs of AMR for other bacteria on dairy farms.

Every year around 800,000 people commit suicide, this represents one death every 40 s. In the search for possible biological biomarkers associated with suicide and/or psychiatric disorders, serum cholesterol levels have been extensively explored. Several studies indicate that cholesterol and associated proteins, especially apolipoproteins (Apos), may play an important role in the diagnosis, prognosis, and susceptibility of suicidal behavior. Here, we describe the current knowledge and findings in the relationship between apolipoproteins and suicide.HIGHLIGHTSThis is the first systematic review of Apos in relation to suicidal behavior.Dysregulations of Apos expression has been observed in patients with suicidal behavior.Apos seem to be associated with cognitive dysfunction in suicide attempters.ApoE is a potential biomarker regarding suicidal behavior.

Background: Monitoring and evaluation of the techniques used in weightlifting are based on the subjective observation of the coach, which can ignore important aspects of short duration. This study aimed to implement an embedded system to register the angular variation of the hip, knee, and ankle joints, and plantar pressure during training., Methods: Four professional and four amateur athletes performed five snatch lifts. To evaluate the angular measurement, the tests were simultaneously videotaped and the results were contrasted., Results: The angular data presented a correlation coefficient of 0.92 and a delay of 495 ± 200 ms. The characterization of the sensors was implemented in a microcontroller with a mean absolute percentage error of 18.8% in the measurements. When comparing the average results between the elite and amateur groups, the amateur group performed a delayed descent in the first three phases of the lift and an accelerated descent in the fourth phase. A not uniform plantar pressure was registered in the same group, causing a reduction in the final speed of recovery with the barbell., Conclusions: The proposed system has been developed for biaxial angular registration of hip, knee, ankle, and plantar pressure during weightlifting snatch. The option to contrast between signals presented by the system met the requirements requested by the coaching staff and is seen as a promising quantitative analysis tool to support the coach and the athlete., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Medical Signals & Sensors.)

Chromosomal instability (CIN), an increased rate of chromosomal segregation abnormalities, drives intratumor heterogeneity and affects most human cancers. In addition to chromosome copy number alterations, CIN results in chromosome(s) (fragments) being mislocalized into the cytoplasm in the form of micronuclei. Micronuclei can be detected by cGAS, a double-strand nucleic acid sensor, which will lead to the production of the second messenger 2'3'-cGAMP, activation of an inflammatory response, and downstream immune cell activation. However, the molecular network underlying the CIN-induced inflammatory response is still poorly understood. Furthermore, there is emerging evidence that cancers that display CIN circumvent this CIN-induced inflammatory response, and thus immune surveillance. The STAT1, STAT3, and NF-κB signaling cascades appear to play an important role in the CIN-induced inflammatory response. In this review, we discuss how these pathways are involved in signaling CIN in cells and how they are intertwined. A better understanding of how CIN is being signaled in cells and how cancer cells circumvent this is of the utmost importance for better and more selective cancer treatment., (© 2023. The Author(s).)

Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of aggressive lymphoma. Approximately 60% of fit patients achieve curation with immunochemotherapy, but the remaining patients relapse or have refractory disease, which predicts a short survival. Traditionally, risk stratification in DLBCL has been based on scores that combine clinical variables. Other methodologies have been developed based on the identification of novel molecular features, such as mutational profiles and gene expression signatures. Recently, we developed the LymForest-25 profile, which provides a personalized survival risk prediction based on the integration of transcriptomic and clinical features using an artificial intelligence system. In the present report, we studied the relationship between the molecular variables included in LymForest-25 in the context of the data released by the REMoDL-B trial, which evaluated the addition of bortezomib to the standard treatment (R-CHOP) in the upfront setting of DLBCL. For this, we retrained the machine learning model of survival on the group of patients treated with R-CHOP (N=469) and then made survival predictions for those patients treated with bortezomib plus R-CHOP (N=459). According to these results, the RB-CHOP scheme achieved a 30% reduction in the risk of progression or death for the 50% of DLBCL patients at higher molecular risk (p-value 0.03), potentially expanding the effectiveness of this treatment to a wider patient population as compared with other previously defined risk groups., Competing Interests: AMO reports honoraria for lectures and participation in advisory boards from Janssen, Takeda, Abbey, Amgen, Novartis, Gilead and AstraZeneca; research grants from Roche, Pfizer and Celgene-BMS and funds for conference organization from Jassen, Takeda, Abbey, Amgen, Novartis, Gilead, Roche, Bristol-Myers-Squibb, Glaxo-Smith-Klyne, Incyte and Pfizer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Mosquera Orgueira, Díaz Arías, Serrano Martín, Portela Piñeiro, Cid López, Peleteiro Raíndo, Bao Pérez, González Pérez, Pérez Encinas, Fraga Rodríguez, Vallejo Llamas and Bello López.)

Introduction: Calcitonine Gen-Related Peptide (CGRP) established a revolution in migraine pathophysiology knowledge and has led to the development of new drugs specifically targeting this disease., Methods: We present a prospective study in which 63 episodic and chronic migraine patients have been treated with anti-CGRP monoclonal antibodies describing their efficacy, security and relapses after their interruption. Response predictors have been analyzed such they can help us to create a better treatment plan., Results: Average age was 48.3 ± 11.81 years old, 84.1% of them being women. The average was of 15.59 migraine days per month (MDM). 63.5% of all patients suffered chronic migraine. The initial dose of Erenumab in all patient was 70 mg subcutaneous. This was increased to 140 mg in 47.6% of the patients. An MDM reduction between 49.85% and 59.53% was obtained within three to twelve months from the start of treatment. Constipation was present in 17.5% of the patients and 4.8% suffered injection site reaction. The treatment was changed to Galcanezumab in 17.9% of the patients. After interrupting the treatment, 23 patients relapsed with a good response on reintroduction of the treatment. It was not possible to establish a clear response predictor, however a statistically significant increase in the number of days of improvement was observed with more MDM at baseline level (p = 0.002)., Conclusions: Anti-CGRP monoclonal antibodies are effective, safe, and well tolerated drugs. We have observed that their discontinuation, in some cases can lead to frequent and early relapses so we strongly recommend to extend the treatment in those patients with a higher MDM., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Mindfulness practice and mindfulness-based interventions are widely known, especially for women's sexuality. However, it is currently unknown how this practice affects the experience of male sexuality, possibly due to the existence of pharmacological treatments that are usually the first choice of treatment for men. The objectives of this study are to explore the influence of mindfulness on different components of men's sexuality from a scoping review of relevant scientific articles existing in the literature. A literature search from 2010 to 2022 was carried out in the electronic databases MEDLINE, Embase, PsycINFO, Web of Science, Scopus, PubMed, Dialnet, SciELO Citation Index, and Redalyc. Out of the 238 studies, 12 that met the defined selection criteria were selected. The analysis of these studies seems to indicate that the practice of mindfulness favours different variables of male sexuality, such as satisfaction and sexual functioning or genital self-image. Mindfulness-based interventions represent a valuable and promising contribution. No adverse effects were detected from the review of scientific articles considered in this work. Nevertheless, more randomized studies with active control groups are necessary to establish the benefits of mindfulness-based interventions in sex therapy for men.

Introduction: Acute plastic deformation refers to a traumatic bending or bowing without a detectable cortical defect., Case Presentation and Discussion: We describe a rare case from an individual that was exhumed from the Hispano-Mudejar necropolis in Uceda (Guadalajara, Spain) dated between the 13th and 14th centuries AD. The case corresponds to an adult woman, with a bowing involvement of the left ulna and radius. After making the differential diagnosis with various pathologies likely to present with this alteration, we reached the diagnosis of acute plastic deformation of the forearm through external and radiological examination and comparison with the healthy contralateral forearm., Conclusions: Acute plastic deformation is a rare traumatic injury, not described until the last century and only rarely described in palaeopathological contexts. We contribute a new case, the first being sufficiently documented, contributing to the knowledge and diagnosis of this type of trauma in the ancient bone, while deepening the knowledge of the living conditions of the medieval Mudejar population of Uceda., (© 2022 S. Karger AG, Basel.)

Human spatial memories are usually evaluated using computer screens instead of real arenas or landscapes where subjects could move voluntarily and use allocentric cues to guide their behavior. A possible approach to fill this gap is the adoption of virtual reality, which provides the opportunity to create spatial memory tasks closer to real-life experience. Here we present and evaluate a new software to create experiments using this technology. Specifically, we have developed a spatial memory task that is carried out in a computer-assisted virtual environment where participants walk around a virtual arena using a joystick. This spatial memory task provides an immersive environment where the spatial component is constantly present without the use of virtual reality goggles. The design is similar to that of tasks used for animal studies, allowing a direct comparison across species. We found that only participants who reported using spatial cues to guide their behavior showed significant learning and performed significantly better during a memory test. This tool allows evaluation of human spatial memory in an ecological environment and will be useful to develop a wide range of other tasks to assess spatial cognition., (© 2021. The Psychonomic Society, Inc.)

Depression is a heterogeneous mental disorder characterized by feelings of sadness and loss of interest that render the subject unable to handle basic daily activities such as sleeping, eating, or working. Neurobiological traits leading to depression include genetic background, early life abuse, life stressors, and systemic and central inflammatory profiles. Several clinical and preclinical reports documented that depression shows an increase in pro-inflammatory markers such as interleukin (IL-)1β, IL-6, IL-12, tumor necrosis factor (TNF), and interferon (IFN)-γ; and a decrease in anti-inflammatory IL-4, IL-10, and transforming growth factor (TGF)-β species. Inflammatory activation may trigger and maintain depression. Dynamic crosstalk between the peripheral immune system and the central nervous system (CNS) such as activated endothelial cells, monocytes, monocyte-derived dendritic cells, macrophages, T cells, and microglia has been proposed as a leading cause of neuroinflammation. Notably, pro-inflammatory cytokines disrupt the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic, noradrenergic, dopaminergic, and glutamatergic neurotransmission. While still under investigation, peripheral cytokines can engage brain pathways and affect the central synthesis of HPA hormones and neurotransmitters through several mechanisms such as activation of the vagus nerve, increasing the permeability of the blood-brain barrier (BBB), altered cytokines transport systems, and engaging toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). However, physiological mechanisms that favor time-dependent central inflammation before or during illness are not totally understood. This review will provide preclinical and clinical evidence of DAMPs and the BBB permeability as contributors to depression and neuroinflammation. We will also discuss pharmacologic approaches that could potentially modulate DAMPs and BBB permeability for future interventions against major depression., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare that they have no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Inflammatory, oxidative, and autoimmune responses cause severe damage to the nervous system inducing loss of myelin layers or demyelination. Even though demyelination is not considered a direct cause of skeletal muscle disease there is extensive damage in skeletal muscles following demyelination and impaired innervation. In vitro and in vivo evidence using exogenous antioxidants in models of demyelination is showing improvements in myelin formation alongside skeletal muscle recovery. For instance, exogenous antioxidants such as EGCG stimulate nerve structure maintenance, activation of glial cells, and reduction of oxidative stress. Consequently, this evidence is also showing structural and functional recovery of impaired skeletal muscles due to demyelination. Exogenous antioxidants mostly target inflammatory pathways and stimulate remyelinating mechanisms that seem to induce skeletal muscle regeneration. Therefore, the aim of this review is to describe recent evidence related to the molecular mechanisms in nerve and skeletal muscle regeneration induced by exogenous antioxidants. This will be relevant to identifying further targets to improve treatments of neuromuscular demyelinating diseases.

Background: The population of South America has been severely affected by the COVID-19 pandemic. In this region, during the year 2020, high seroprevalence percentages were reported, which have been associated with the socioeconomic characteristics of the population, mainly in urban areas. However, a relative lack of information on the dynamics of the pandemic in rural areas of these countries, where the population is more vulnerable, is still present. This study determined antibody prevalence against SARS-CoV-2 in urban and rural food producing workers in Colombia., Methods: A total of 1242 workers, urban and rural, linked to poultry, dairy, and meat production and supply chains, were analyzed through a sociodemographic survey and two serological tests against S and N proteins of SARS-CoV-2., Results: 78.7% were male. 50.9% of the participants were rural inhabitants, with an average age of 40.9 years old. 39.2% had IgM and IgG against SARS-CoV-2 S protein and 31.3% against N protein for the same virus; 83.6% had not been tested with an RT-PCR test for COVID-19 and 75.7% did not report symptoms related to the disease. The associated risk factors were low education, OR: 1.46, greater number of cohabitants, OR: 1.36, and contact with people infected with COVID-19, OR: 2.03., Conclusions: The seroprevalences found suggest an important interconnectivity between rural and urban areas, where asymptomatic subjects and sociodemographic factors facilitate the virus' spread in the population., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors.)

Background: Primary Sjögren syndrome (pSS) is a chronic autoimmune disease with its main target being exocrine glands, and is the connective tissue disease more frequently associated with other autoimmune diseases. The aim of this study was to assess the frequency of another autoimmune rheumatic disease (ARD) developed in primary Sjögren syndrome (pSS) patients and to describe it's clinical, serological and histologic characteristics., Materials and Methods: This is a retrospective cohort study. Data of patients with pSS diagnosis (American-European criteria 2002), included in the GESSAR database (Grupo de Estudio Síndrome de Sjögren, Sociedad Argentina de Reumatología) were analyzed. The development of a second ARD was registered during the follow up., Results: 681 patients were included, 94.8% female. The mean age was 54 (SD 14) years and mean age at diagnosis of 50 (SD 13) years. The mean follow-up was 4.7 (SD 4.9) years; 30 patients (4.41%, CI 95%: 3.1-5.7) developed a second ARD during the follow up, incidence rate was 9.1/1000 patients-year (IR 95%: 5.8-12.4/1000 patients-year), the most frequent being rheumatoid arthritis (RA). 96% out of these 30 patients had xerophthalmia, 86.2% xerostomia, 92% positive Schirmer test, 88.24% positive Rosa Bengala test, lisamine green or Ocular Staining Score, 81.2% positive unstimulated salivary flow, 82.1% Ro(+) and 33.33% La(+). Minor salivary gland biopsy had been performed in 14 of the 30 patients, 12 with positive results. There were no statistically significant differences respect baseline characteristics when comparing the patients who developed another ARD to the ones that did not., Conclusions: Of all the patients analyzed, 4.4% presented another ARD during their follow-up. It is important to be aware of this, to make an early and proper diagnosis and treatment of our patients., (© 2022. The Author(s).)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Despite notable therapeutic advances in the last decades, 30%-40% of affected patients develop relapsed or refractory disease that frequently precludes an infamous outcome. With the advent of new therapeutic options, it becomes necessary to predict responses to the standard treatment based on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). In a recent communication, we presented a new machine learning model (LymForest-25) that was based on 25 clinical, biochemical, and gene expression variables. LymForest-25 achieved high survival prediction accuracy in patients with DLBCL treated with upfront immunochemotherapy. In this study, we aimed to evaluate the performance of the different features that compose LymForest-25 in a new UK-based cohort, which contained 481 patients treated with upfront R-CHOP for whom clinical, biochemical and gene expression information for 17 out of 19 transcripts were available. Additionally, we explored potential improvements based on the integration of other gene expression signatures and mutational clusters. The validity of the LymForest-25 gene expression signature was confirmed, and indeed it achieved a substantially greater precision in the estimation of mortality at 6 months and 1, 2, and 5 years compared with the cell-of-origin (COO) plus molecular high-grade (MHG) classification. Indeed, this signature was predictive of survival within the MHG and all COO subgroups, with a particularly high accuracy in the "unclassified" group. Integration of this signature with the International Prognostic Index (IPI) score provided the best survival predictions. However, the increased performance of molecular models with the IPI score was almost exclusively restricted to younger patients (<70 y). Finally, we observed a tendency towards an improved performance by combining LymForest-25 with the LymphGen mutation-based classification. In summary, we have validated the predictive capacity of LymForest-25 and expanded the potential for improvement with mutation-based prognostic classifications., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Follicular Lymphoma (FL) has a 10-year mortality rate of 20%, and this is mostly related to lymphoma progression and transformation to higher grades. In the era of personalized medicine it has become increasingly important to provide patients with an optimal prediction about their expected outcomes. The objective of this work was to apply machine learning (ML) tools on gene expression data in order to create individualized predictions about survival in patients with FL. Using data from two different studies, we were able to create a model which achieved good prediction accuracies in both cohorts (c-indexes of 0.793 and 0.662 in the training and test sets). Integration of this model with m7-FLIPI and age rendered high prediction accuracies in the test set (cox c-index 0.79), and a simplified approach identified 4 groups with remarkably different outcomes in terms of survival. Importantly, one of the groups comprised 27.35% of patients and had a median survival of 4.64 years. In summary, we have created a gene expression-based individualized predictor of overall survival in FL that can improve the predictions of the m7-FLIPI score., Competing Interests: AO has received honoraria for lectures and participation in advisory boards from Janssen and AstraZeneca. AO has received research grants from Roche and Celgene-BMS. JL has received honoraria for lectures and participation in advisory boards from Janssen, Abbey and Roche. JL has received research funds from Roche and Celgene-BMS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GS declared a shared affiliation with one of the authors CC, to the handling editor at time of review., (Copyright © 2022 Mosquera Orgueira, Cid López, Peleteiro Raíndo, Abuín Blanco, Díaz Arias, González Pérez, Antelo Rodríguez, Bao Pérez, Ferreiro Ferro, Aliste Santos, Pérez Encinas, Fraga Rodríguez, Cerchione, Mozas and Bello López.)

Introduction: The objective of the study was to explore the effect of the Mindfulness-based program (MBSR) on the sexual health and psychological well-being of professionals and volunteers of Doctors of the World who care for people at risk of social exclusion., Method: The entire population of a NGO in southern Spain was chosen because it receives a large number of vulnerable people. Quasi-experimental study with pre and post-test measurements. The intervention lasted 8weeks plus an introductory session, with sessions of 2.5h. Seven instruments were applied before and after the intervention: (a) Mindfulness Scale (MAAS); (b) Body Connection Scale; (c) Compassion Questionnaire (SCS); (d) Ryff's psychological well-being scale; (e) Hurlbert's Fantastic Sexuality Index; (f) Wilson's Sexual Fantasy Scale, and (g) Hudson's Sexual Satisfaction Index (ISS)., Results: Most of the post-test scores were better compared to the pre-test. On the MAAS scale, the score was higher in the post-test than in the pretest (Wilcoxon=-2668, P<.05) and, in the ISS, the score was also higher in the post-test than in the pre-test (Wilcoxon=-2.201, P<.05). However, in the Bodily Dissociation subscale, the score was lower (Wilcoxon=-2.670, P<.05). All effect sizes were moderate to high., Conclusions: The application of the MBSR protocol can increase the degree of sexual satisfaction, decrease body dissociation, promote mental health and self-compassion in people who treat vulnerable people, which may have an impact on a higher quality of approach to them., (Copyright © 2021 Asociación Española de Andrología, Medicina Sexual y Reproductiva. Publicado por Elsevier España, S.L.U. All rights reserved.)

Rare bleeding disorders (RBDs) comprise the inherited deficiencies of coagulation factors such as fibrinogen, factor (F)II, FV, FV fl FVIII, FVII, FX, FXI, and FXIII, and are usually transmitted as autosomal recessive disorders. Given the low prevalence of these coagulopathies, information about their genetic, clinical and laboratory characteristics is limited. The clinical symptoms of RCDs are extremely diverse in terms of bleeding type, site, severity, age at onset, and duration. The weak association between residual coagulant activity and clinical bleeding severity, or at times inexistent, correlation between the factor's residual levels and clinical manifestations in some RBDs makes it difficult to use a single criterion to classify such conditions. Standardization and customization of coagulation assays, full genome sequencing, and global clotting assays will significantly improve diagnosis of patients with RBDs., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To estimate the burden of disease through 4 complementary procedures to years lived with disability (YLDs) using the concept of attributable fraction and including analysis of subdomains of disability., Methods: We explored the burden on disability for 7 common musculoskeletal disorders (CMD) using the 2009 to 2010 Chilean National Health Survey, which included the Community Oriented Programme for the Control of Rheumatic Disease Core Questionnaire to identify cases with CMD, and an 8-domain questionnaire for health state descriptions. We calculated the proportion of disability attributable to pain in the general population and people with CMD. We also estimated the burden of CMD expressed as YLD and as the proportion of the disability in the general population attributable to people with CMD, with a particular focus in the pain domain of disability. Second order of uncertainty around point estimations was also characterized., Results: Pain domain of disability accounted for 23.4% of the total disability in the general population, and between 20% (fibromyalgia) to 27.1% (osteoarthritis of the hip) in people with some of the selected CMD. People with chronic musculoskeletal pain accounted for 21.2% of total disability from general population, which generated 1.2 million of YLD (6679 YLD/100 000 inhabitants). Chronic low back pain and osteoarthritis of the knee were in the top position of specific CMDs, explaining the highest national burden., Conclusion: Pain is an essential component of disability in people with CMD and also in the general population. The approach used can be easily applied to other health conditions and other domains of disability., (Copyright © 2021. Published by Elsevier Inc.)

B-cell lymphoproliferative disorders exhibit a diverse spectrum of diagnostic entities with heterogeneous behaviour. Multiple efforts have focused on the determination of the genomic drivers of B-cell lymphoma subtypes. In the meantime, the aggregation of diverse tumors in pan-cancer genomic studies has become a useful tool to detect new driver genes, while enabling the comparison of mutational patterns across tumors. Here we present an integrated analysis of 354 B-cell lymphoid disorders. 112 recurrently mutated genes were discovered, of which KMT2D, CREBBP, IGLL5 and BCL2 were the most frequent, and 31 genes were putative new drivers. Mutations in CREBBP, TNFRSF14 and KMT2D predominated in follicular lymphoma, whereas those in BTG2, HTA-A and PIM1 were more frequent in diffuse large B-cell lymphoma. Additionally, we discovered 31 significantly mutated protein networks, reinforcing the role of genes such as CREBBP, EEF1A1, STAT6, GNA13 and TP53, but also pointing towards a myriad of infrequent players in lymphomagenesis. Finally, we report aberrant expression of oncogenes and tumor suppressors associated with novel noncoding mutations (DTX1 and S1PR2), and new recurrent copy number aberrations affecting immune check-point regulators (CD83, PVR) and B-cell specific genes (TNFRSF13C). Our analysis expands the number of mutational drivers of B-cell lymphoid neoplasms, and identifies several differential somatic events between disease subtypes., Competing Interests: The authors declare no conflicts of interest.

Competing Interests: Conflicts of interest None disclosed.

There is growing evidence indicating the implication of germline variation in cancer predisposition and prognostication. Here, we describe an analysis of likely disruptive rare variants across the genomes of 726 patients with B-cell lymphoid neoplasms. We discovered a significant enrichment for two genes in rare dysfunctional variants, both of which participate in the regulation of oxidative stress pathways ( CHMP6 and GSTA4 ). Additionally, we detected 1675 likely disrupting variants in genes associated with cancer, of which 44.75% were novel events and 7.88% were protein-truncating variants. Among these, the most frequently affected genes were ATM , BIRC6 , CLTCL1A , and TSC2 . Homozygous or germline double-hit variants were detected in 28 cases, and coexisting somatic events were observed in 17 patients, some of which affected key lymphoma drivers such as ATM , KMT2D , and MYC . Finally, we observed that variants in six different genes were independently associated with shorter survival in CLL. Our study results support an important role for rare germline variation in the pathogenesis and prognosis of B-cell lymphoid neoplasms.

Objective: Compare the diagnostic properties of five case definitions of suspected COVID-19 that were used or proposed in Chile during the first eight months of the pandemic., Methods: An analysis was done of the diagnostic properties (sensitivity, specificity, and positive and negative predictive values) of three case definitions of suspected COVID-19 used in Chile between March and October 2020, as well as two alternative proposed definitions. The sample was 2,019 people with known results for the polymerase chain reaction (PCR) test for SARS-CoV-2. Stepwise logistic regression was used to develop criterion 5, optimizing sensitivity and specificity values. Multifactor logistic regression was used to explore the association between demographic variables, symptoms and signs, and PCR positivity. Different positivity scenarios were analyzed and ROC curves were compared., Results: The presence of anosmia (OR = 8.00; CI95%: 5.34-11.99), fever (OR = 2.15; CI95%: 1.28-3.59), and having been in close contact with a person sick with COVID-19 (OR = 2.89; CI95%: 2.16-3.87) were associated with a positive PCR result. According to the analysis of the ROC curve, criterion 5 had the highest capacity for discrimination, although there were no significant differences with the other four criteria., Conclusions: Criterion 5-based on anosmia, close contact with people with COVID-19, and fever as sufficient unique elements-was the most sensitive in identifying suspected cases of COVID-19, a key aspect in controlling the spread of the pandemic.

As the identification and targeting of salient risk factors for adolescent substance use become more widely used globally, an essential question arises as to whether U.S.-based cut points in the distributions of these risk factors that identify "high" risk can be used validly in other countries as well. This study examined proportions of youth at "high" risk using different empirically derived cut points in the distributions of 18 measured risk factors. Data were obtained from large-scale samples of adolescents in Colombia and the United States. Results indicated that significant ( p < 0.05) differences in the proportions of "high" risk youth were found in 38.9% of risk factors for 6th graders, 61.1% for 8th graders, and 66.6% for 10th graders. Colombian-based cut points for determining the proportion of Colombian youth at "high" risk were preferable to U.S.-based cut points in almost all comparisons that exhibited a significant difference. Our findings suggest that observed differences were related to the type of risk factor (e.g., drug specific vs. non-drug specific). Findings from this study demonstrate the need for collecting large-scale national data on risk factors for adolescent substance use and developing country-specific cut points based on the distributions of these measures to avoid misidentification of youth at "high" risk.

Background: Thirty to forty percent of patients with Diffuse Large B-cell Lymphoma (DLBCL) have an adverse clinical evolution. The increased understanding of DLBCL biology has shed light on the clinical evolution of this pathology, leading to the discovery of prognostic factors based on gene expression data, genomic rearrangements and mutational subgroups. Nevertheless, additional efforts are needed in order to enable survival predictions at the patient level. In this study we investigated new machine learning-based models of survival using transcriptomic and clinical data., Methods: Gene expression profiling (GEP) of in 2 different publicly available retrospective DLBCL cohorts were analyzed. Cox regression and unsupervised clustering were performed in order to identify probes associated with overall survival on the largest cohort. Random forests were created to model survival using combinations of GEP data, COO classification and clinical information. Cross-validation was used to compare model results in the training set, and Harrel's concordance index (c-index) was used to assess model's predictability. Results were validated in an independent test set., Results: Two hundred thirty-three and sixty-four patients were included in the training and test set, respectively. Initially we derived and validated a 4-gene expression clusterization that was independently associated with lower survival in 20% of patients. This pattern included the following genes: TNFRSF9, BIRC3, BCL2L1 and G3BP2. Thereafter, we applied machine-learning models to predict survival. A set of 102 genes was highly predictive of disease outcome, outperforming available clinical information and COO classification. The final best model integrated clinical information, COO classification, 4-gene-based clusterization and the expression levels of 50 individual genes (training set c-index, 0.8404, test set c-index, 0.7942)., Conclusion: Our results indicate that DLBCL survival models based on the application of machine learning algorithms to gene expression and clinical data can largely outperform other important prognostic variables such as disease stage and COO. Head-to-head comparisons with other risk stratification models are needed to compare its usefulness.

A series of GdCu 2 nanoparticles with controlled sizes ranging from 7 nm to 40 nm has been produced via high-energy inert-gas ball milling. Rietveld refinements on the X-ray diffraction measurements ensure that the bulk crystalline I m m a structure is retained within the nanoparticles, thanks to the employed low milling times ranging from t = 0.5 to t = 5 h. The analysis of the magnetic measurements shows a crossover from Superantiferromagnetism (SAF) to a Super Spin Glass state as the size decreases at NP size of 〈 D 〉 ≈ 18 nm. The microstrain contribution, which is always kept below 1%, together with the increasing surface-to-core ratio of the magnetic moments, trigger the magnetic disorder. Additionally, an extra contribution to the magnetic disorder is revealed within the SAF state, as the oscillating RKKY indirect exchange achieves to couple with the aforementioned contribution that emerges from the size reduction. The combination of both sources of disorder leads to a maximised frustration for 〈 D 〉 ≈ 25 nm sized NPs.

Communities That Care (CTC) is a prevention system aimed at reducing antisocial behaviors in adolescents. In Colombia, this system has been developed and adapted under the name of Comunidades Que se Cuidan (CQC). Successful implementation of CQC depends on valid associations between measured risk and protective factors (RPFs) for substance use and substance use outcomes. This study assessed these associations using large-scale, school-based surveys of Colombian youth. A cross-sectional analysis was performed. Data from 23 communities in Colombia were collected between 2012 and 2016 from young people (N = 50,946) aged 10 to 19 years. Dichotomous alcohol, cigarette, cannabis, and other illegal drug use outcomes were assessed for past 30-day, past-year, and lifetime use. Logistic regression analyses, adjusting for age, gender, and age by RPF, and gender by RPF interactions, were performed for each RPF. All the associations of the 14 RPF evaluated were statistically significant (p<,001). Regarding observed effect sizes, 3.0% were considered very small (0.70 ≥ OR ≤ 1.43), 51.7% small (0.70 ≥ OR ≥ 1.43), 42.6% medium (0.40 ≥ OR ≥ 2.48) and 7.1% large (0.23 ≥ OR ≥ 4.27). Significant main effects for age and gender, and their interactions with RPFs were found for most RPFs. Findings from this study demonstrate the viability of RPFs for adolescent substance use as focal points for intervention planning, development, and evaluation of community-based prevention systems like CQC that rely on epidemiologic data for local decision making.

Values and preferences relate to the importance that patients place on health outcomes (eg, bleeding, having a deep venous thrombosis) and are essential when weighing benefits and harms in guideline recommendations. To inform the American Society of Hematology guidelines for management of venous thromboembolism (VTE) disease, we conducted a systematic review of patients' values and preferences related to VTE. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature from inception to April of 2018 (PROSPERO-CRD42018094003). We included quantitative and qualitative studies. We followed Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance for rating the certainty and presenting findings for quantitative research about the relative importance of health outcomes and a grounded theory approach for qualitative thematic synthesis. We identified 14 quantitative studies (2465 participants) describing the relative importance of VTE-related health states in a widely diverse population of patients, showing overall small to important impact on patients' lives (certainty of the evidence from low to moderate). Additionally, evidence from 34 quantitative studies (6424 participants) and 15 qualitative studies (570 participants) revealed that patients put higher value on VTE risk reduction than on the potential harms of the treatment (certainty of evidence from low to moderate). Studies also suggested a clear preference for oral medication over subcutaneous medication (moderate certainty). The observed variability in health state values may be a result of differences in the approaches used to elicit them and the diversity of included populations rather than true variability in values. This finding highlights the necessity to explore the variability induced by different approaches to ascertain values., (© 2020 by The American Society of Hematology.)

Heavy metal pollution has become an environmental and health problem worldwide. With the aim of finding novel strategies for metal bioremediation, endophytic fungi from the heavy metal hyperaccumulator plant Vachellia farnesiana were isolated and characterized. The plants were growing in mine tailings, rich in Zn, Pb, and Cu. Morphological and phylogenetic analyses indicated that the fungal strains belonged to Neocosmospora and Aspergillus genera. The Neocosmospora isolate belongs to the Fusarium solani species complex (FSSC) that groups phytopathogen species. However, in this case the plants from which it was isolated did not show any signs of disease. Both fungal strains were able to remove significant amounts of heavy metals from liquid cultures, either in a mixture of the three metals or each metal in a single culture. In response to lead exposure, the Neocosmospora sp. strain secreted specific novel phenolic compounds other than anthraquinones or naphtoquinones, which have been described in similar situations. The Aspergillus sp. dropped the pH in the medium. High-performance liquid chromatography determinations indicated that this strain secreted mainly glutamic acid in response to lead, a novel mechanism, which has not been reported elsewhere. Malic and succinic acids were also produced in response to lead exposure. Possibly, glutamic and succinic acids (synthesized in the Krebs cycle) can be used to cope with metal toxicity due to the plant providing photosynthates to the fungus. These fungi showed the potential to be used for bioremediation or restoration of metal-polluted environments., Competing Interests: The authors declare no conflict of interest.

In this paper the current regulations on cadaveric preservation practices required for the transfer of corpses in the different Autonomous Communities -Reglamentos de Policía Sanitaria Mortuoria- and national legislation are compared. The criteria taken into account have been: a) which sanitary practices are included in the regulations, b) which ones can be carried out in corpses posing a health risk, c) when they are compulsory to be carried out, d) when they can be carried out after death, and e) what professionals can carry them out and/or take responsibility for them. At the time of finishing the paper, a new mortuary regulation is being passed in Andalusia, as well as a decree from the Ministry of Health on technical and sanitary requirements concerning international transfer of corpses and human remains.