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Honey differentiation based on the botanical origin is crucial to guarantee product authenticity, especially considering the increasing number of fraud cases. This study assessed the metabolomic differences arising from various botanical origins in honey products sold in Spanish markets, focusing on two goals: (1) discrimination within monofloral samples (eucalyptus, rosemary, and orange blossom honey) and (2) differentiation between multifloral vs. monofloral honey samples. An omics strategy based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap-high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) was applied for the reliable identification of specific honey markers selected by orthogonal partial least squares discriminant analysis (OPLS-DA) (R 2 Y = 0.929-0.981 and Q 2 = 0.868-0.952), followed by the variable importance in projection (VIP) approach. Key amino acid, alkaloid, and trisaccharide markers were identified to distinguish between honey samples. Some Amadori compounds were highlighted as eucalyptus honey markers, suggesting their potential use for honey aging and botanical origin differentiation. L-phenylalanine and raffinose were markers of rosemary honey. Four markers (e.g., trigonelline, L-isoleucine, and N -(1-deoxy-1-fructosyl)isoleucine) were found in higher levels in multifloral samples, indicating a greater availability of amino acids, potentially increasing the Maillard reaction. This research is the first to address the botanical origin's impact on honey by identifying novel markers not previously described.

Colombia hosts the largest number of refugees and migrants fleeing the humanitarian emergency in Venezuela, many of whom experience high levels of displacement-related trauma and adversity. Yet, Colombian mental health services do not meet the needs of this population. Scalable, task-sharing interventions, such as Group Problem Management Plus (Group PM+), have the potential to bridge this gap by utilizing lay workers to provide the intervention. However, the current literature lacks a comprehensive understanding of how and for whom Group PM+ is most effective. This mixed methods study utilized data from a randomized effectiveness-implementation trial to examine the mediators and moderators of Group PM+ on mental health outcomes. One hundred twenty-eight migrant and refugee women in northern Colombia participated in Group PM+ delivered by trained community members. Patterns in moderation effects showed that participants in more stable, less marginalized positions improved the most. Results from linear regression models showed that Group PM+-related skill acquisition was not a significant mediator of the association between session attendance and mental health outcomes. Participants and facilitators reported additional possible mediators and community-level moderators that warrant future research. Further studies are needed to examine mediators and moderators contributing to the effectiveness of task-shared, scalable, psychological interventions in diverse contexts., Competing Interests: P.V. is a staff member of the United Nations. The views expressed in this editorial are those of the authors and do not necessarily reflect the views of the United Nations. All other authors maintain that there are no conflicts of interest to disclose.

Infantile hemangioma is a benign vascular tumor, the most common in childhood, whose natural evolution is the disappearance of the lesion in the pediatric age and which has effective and safe treatments that limit its growth and favor its disappearance at younger ages. Infantile hemangioma continues to be a reason for attention to complications, due to erroneous diagnoses, lack of knowledge of the condition, late referral or fear of the effects of the medications used for its treatment. Furthermore, its presence is normalized without taking into account that it can cause uncertainty, anxiety, feelings of guilt and, as a consequence, a significant impact on the quality of life, mainly in the parents or caregivers of the child. The need for a clinical practice guideline in our country arises from the high presentation of late-remitted complications in infantile hemangioma even with the availability of adequate treatments, the continuous evolution of medicine and the appearance of new evidence. Throughout the guide you will find recommendations regarding the diagnosis, treatment and follow-up of patients with infantile hemangioma, taking into account the paraclinical tests that can be performed, topical or systemic management options, as well as adjuvant therapies. For the first time, objective tools for patient follow-up are included in a guide for the management of infantile hemangioma, as well as to help the first contact doctor in timely referral., (Copyright: © 2024 Permanyer.)

Objectives: The objective of this study was to compare the rate of post-operative radiation therapy (PORT) initiation within 6 weeks for head and neck squamous cell carcinoma patients treated at a safety net, academic institutio between 2019 and 2021 versus those treated in 2022 after implementation of a new clinical pathway., Methods: A retrospective case-control study was performed at a single tertiary care, safety-net, academic institution. Patient demographics, tumor characteristics, dates of surgery, and other treatment dates were collected from the electronic medical record. The time from surgery to PORT was calculated. Patients who started radiation treatment within 42 days of surgery were regarded as having started PORT on time. The demographics, tumor characteristics, and rate of timely PORT for the two cohorts of patients were compared., Results: From 2018 to 2021, our rate of PORT initiation within 6 weeks of surgery was 12% ( n  = 57). In 2022, our rate of timely PORT was 88% ( n  = 16), p  < 0.5. Patient demographics and characteristics were similar with the exception of marital status and use of free-flap reconstruction. The 2022 cohort was more likely to be single ( p  < 0.5), and all patients underwent free-flap reconstruction in 2022 ( p  < 0.05)., Conclusion: Early referrals, frequent communication, and use of a secure registry were the key to the success found by our group despite the socioeconomic challenges of our underserved, safety-net hospital patient population. The changes made at our institution should serve as a template for other institutions seeking to improve the quality of care for their HNSCC patients., Competing Interests: The authors report no conflicts of interest for the existing work., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Failed back surgery syndrome (FBSS) is a common and incapacitating condition affecting patients with previous spine surgery in whom treatment approach can be challenging. This study aimed to summarize existing secondary studies and up-to-date randomized clinical trials (RCTs) that assess the effectiveness of available treatment options for FBSS., Methods: Systematic searches were carried out in five databases (PubMed, Cochrane, Scielo, Epistemonikos, and Google scholar) for all systematic reviews on the effectiveness of treatment options for FBSS published after 2012. Outcomes of interest were pain levels measured through visual analog scale or numeric rating scale, Oswestry Disability Index, and quality of life. Methodological and risk of bias assessments were performed with the AMSTAR-2 tool for systematic reviews and the Joanna Briggs Institute checklist for RCT. Prospective PROSPERO registration: CRD42022307609., Results: Fifteen studies, seven systematic reviews, and eight RCTs met the inclusion criteria and fulfilled the methodological quality assessment. Of the 15 included studies, 8 were on neurostimulation, 4 on adhesiolysis, 4 on epidural or intrathecal injections, and 3 on other treatment modalities. The risk of bias was low in seven studies, moderate in five, and high in three., Conclusions: Based on this systematic overview and the considerable heterogeneity among studies, the FBSS therapeutic approach must be individualized. FBSS treatment should start with conservative management, considering the implementation of neurostimulation, a technique with the most robust evidence of effective results, in cases of refractory axial or neuropathic pain. As the last resource, in light of the evidence found, more invasive procedures or new surgical interventions are indicated., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2024 The Japanese Society for Spine Surgery and Related Research.)

Fragile X syndrome is caused by the expansion of CGG triplets in the FMR1 gene, which generates epigenetic changes that silence its expression. The absence of the protein coded by this gene, FMRP, causes cellular dysfunction, leading to impaired brain development and functional abnormalities. The physical and neurologic manifestations of the disease appear early in life and may suggest the diagnosis. However, it must be confirmed by molecular tests. It affects multiple areas of daily living and greatly burdens the affected individuals and their families. Fragile X syndrome is the most common monogenic cause of intellectual disability and autism spectrum disorder; the diagnosis should be suspected in every patient with neurodevelopmental delay. Early interventions could improve the functional prognosis of patients with Fragile X syndrome, significantly impacting their quality of life and daily functioning. Therefore, healthcare for children with Fragile X syndrome should include a multidisciplinary approach., Competing Interests: Conflict of interest: R.H. is a member of the Scientific and Clinical advisory committee of the National Fragile X Foundation (NFXF), R.H. is on the Clinical Treatments Committee of the NFXF, and R.H is on Zynerba Scientific Advisory Committee. In addition, RH has received funding from the Azrieli Foundation and Zynerba Pharmaceuticals to carry out treatment trials in Fragile X syndrome.The other authors have no conflict of interest., (Copyright © 2023 Colombia Medica.)

Mg-Zn co-dopedGaN powders via the nitridation of a Ga-Mg-Zn metallic solution at 1000 °C for 2 h in ammonia flow were obtained. XRD patterns for the Mg-Zn co-dopedGaN powders showed a crystal size average of 46.88 nm. Scanning electron microscopy micrographs had an irregular shape, with a ribbon-like structure and a length of 8.63 µm. Energy-dispersive spectroscopy showed the incorporation of Zn (Lα 1.012 eV) and Mg (Kα 1.253 eV), while XPS measurements showed the elemental contributions of magnesium and zinc as co-dopant elements quantified in 49.31 eV and 1019.49 eV, respectively. The photoluminescence spectrum showed a fundamental emission located at 3.40 eV(364.70 nm), which was related to band-to-band transition, besides a second emission found in a range from 2.80 eV to 2.90 eV (442.85-427.58 nm), which was related to a characteristic of Mg-doped GaN and Zn-doped GaN powders. Furthermore, Raman scattering demonstrated a shoulder at 648.05 cm -1 , which could indicate the incorporation of the Mg and Zn co-dopants atoms into the GaN structure. It is expected that one of the main applications of Mg-Zn co-doped GaN powders is in obtaining thin films for SARS-CoV-2 biosensors.

The effect of the deposit temperature of zinc oxide (ZnO) doped with nickel (Ni) by hot filament chemical vapor deposition (HFCVD) technique is reported in this work. The technique allows depositing ZnO:Ni in short intervals (1 min). A deposit of undoped ZnO is used as a reference sample. The reference sample was deposited at 500 °C. The ZnO:Ni samples were deposited at 500 °C, 400 °C, 350 °C, and 300 °C. The samples were studied using structural, morphological, and optical characterization techniques. The Ni incorporation to the ZnO lattice was verified by the shift of the X-ray diffraction peaks, the Raman peaks, the band gap, and the photoluminescence measurements. It was found that the deposit temperature affects the structural, morphological, and optical properties of the ZnO:Ni samples too. The structure of the ZnO:Ni samples corresponds to the hexagonal structure. Different microstructures shapes such as spheres, sea urchins, and agglomerate were found in samples; their change is attributed to the deposit temperature variation. The intensity of the photoluminescence of the ZnO:Ni improves concerning the ZnO due to the Ni incorporation, but it decreases as the deposit temperature decreases.

With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.

Background: Mental disorders are one of the main causes of years lived with disability, although there is a lack of recent estimates of their magnitude., Objective: To report the trends of mental disorders prevalence, years lived with disability and years of healthy life lost by sex, age and state in Mexico., Material and Methods: The Global Burden of Disease database for Mexico was used., Results: There were an estimated 18.1 million persons with some mental disorder in 2021, which represented an increase of 15.4% in comparison with 2019. Depressive and anxiety disorders did significantly increase between 2019 and 2021, which is possibly related to COVID-19, the confinement and the situations of grief experienced during the pandemic., Conclusions: Mental disorders have considerably increased since the only national mental health survey that used diagnostic criteria to evaluate their prevalence. It is important to invest in epidemiological studies, prevention and care of mental disorders, which are among the leading causes of years lived with disability in the country., (Copyright: © 2023 Permanyer.)

Background: Pigmented (or melanocytic) neurofibroma (PN) constitutes only 1% of cases and is considered a rare variant of neurofibroma containing melanin-producing cells. In addition, the association of PN with hypertrichosis is infrequent., Case Report: We describe the case of an 8-year-old male with a neurofibromatosis type 1 (NF1) diagnosis, who presented a light brown hyperpigmented plaque, smooth and well-demarcated, and hypertrichosis on the left thigh. The skin biopsy showed characteristics of neurofibroma; however, in the deep portion of the lesion, melanin deposits positive for S100, Melan-A, and HMB45 were observed, thus establishing the diagnosis of pigmented neurofibroma., Conclusions: Although PN is a rare subtype of neurofibroma, it is considered a chronically progressive benign tumor containing melanin-producing cells. These lesions can appear alone or in association with neurofibromatosis. Since this is a tumor that can be confused with other skin lesions, biopsy analysis is essential to differentiate it from other pigmented skin tumors, such as melanocytic schwannoma, dermatofibrosarcoma protuberans, neurocristic hamartoma, or neuronevus. Surveillance is part of the treatment, and surgical resection is sometimes performed., (Copyright: © 2023 Permanyer.)

FMR1 premutation cytosine-guanine-guanine repeat expansion alleles are relatively common mutations in the general population that are associated with a neurodegenerative disease (fragile X-associated tremor/ataxia syndrome), reproductive health problems and potentially a wide range of additional mental and general health conditions that are not yet well-characterised. The International Fragile X Premutation Registry (IFXPR) was developed to facilitate and encourage research to better understand the FMR1 premutation and its impact on human health, to facilitate clinical trial readiness by identifying and characterising diverse cohorts of individuals interested in study participation, and to build community and collaboration among carriers, family members, researchers and clinicians around the world. Here, we describe the development and content of the IFXPR, characterise its first 747 registrants from 32 countries and invite investigators to apply for recruitment support for their project(s). With larger numbers, increased diversity and potentially the future clinical characterisation of registrants, the IFXPR will contribute to a more comprehensive and accurate understanding of the fragile X premutation in human health and support treatment studies., Competing Interests: Competing interests: DH is a member of the Clinical and Scientific Advisory Committee and the Clinical Trials Committee of the National Fragile X Foundation., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This work presents the theoretical calculation of isotherm diagrams for quaternary alloys of III-V semiconductor compounds with the form III x III 1-x V y V 1-y . In particular, the isotherm diagrams for the Al x Ga 1-x As y Sb 1-y quaternary alloy at low temperatures were calculated (500 °C, 450 °C, 400 °C, and 350 °C). The Al x Ga 1-x As y Sb 1-y quaternary alloy was formed from four binary compounds such as GaAs, AlAs, AlSb, and GaSb, all with direct bandgaps. The regular solution approximation was used to find the quaternary isotherm diagrams, represented in four linearly independent equations, which were solved using Parametric Technology Corporation Mathcad 14.0 software for different arsenic and antimony atomic fractions. The results support the possible growth of layers via liquid-phase epitaxy in a range of temperatures from 500 °C to 350 °C, where the crystalline quality could be improved at low temperatures. These semiconductor layers could have applications for optoelectronic devices in photonic communications, thermophotovoltaic systems, and microwave devices with good crystalline quality.

The Amazon forest has the highest biodiversity on Earth. However, information on Amazonian vertebrate diversity is still deficient and scattered across the published, peer-reviewed, and gray literature and in unpublished raw data. Camera traps are an effective non-invasive method of surveying vertebrates, applicable to different scales of time and space. In this study, we organized and standardized camera trap records from different Amazon regions to compile the most extensive data set of inventories of mammal, bird, and reptile species ever assembled for the area. The complete data set comprises 154,123 records of 317 species (185 birds, 119 mammals, and 13 reptiles) gathered from surveys from the Amazonian portion of eight countries (Brazil, Bolivia, Colombia, Ecuador, French Guiana, Peru, Suriname, and Venezuela). The most frequently recorded species per taxa were: mammals: Cuniculus paca (11,907 records); birds: Pauxi tuberosa (3713 records); and reptiles: Tupinambis teguixin (716 records). The information detailed in this data paper opens up opportunities for new ecological studies at different spatial and temporal scales, allowing for a more accurate evaluation of the effects of habitat loss, fragmentation, climate change, and other human-mediated defaunation processes in one of the most important and threatened tropical environments in the world. The data set is not copyright restricted; please cite this data paper when using its data in publications and we also request that researchers and educators inform us of how they are using these data., (© 2022 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Background: Rothmund-Thomson syndrome, also known as congenital poikiloderma, is a rare autosomal recessive genodermatosis with onset in early childhood that affects at a multisystem level., Case Reports: Case 1. A 4-year-old male patient, consanguineous parents, 26-year-old brother with a probable diagnosis of Rothmund-Thompson syndrome. He presented with adactyly of the right thumb, hypoplasia of the left thumb, delayed growth and psychomotor development. At 3 months, he presented rough, dry, sparse hair and erythematous lesions on the face, leaving hyperpigmented and hypopigmented spots with a reticulated pattern. We detected hypoacusis, skeletal alterations, narrow chin, short stature, severe malnutrition, and chronic and asymptomatic hypodontia. Genetic sequencing showed a mutation for the RECQL4 gene, for which a multidisciplinary follow-up was provided by the genetics, gastroenterology, nutrition, endocrinology, stomatology, audiology, orthopedics, rehabilitation, ophthalmology and oncology services. Case 2. A 2-year-old female patient presented facial erythema that spread to the arms and legs at 3 months; skin biopsy showed poikiloderma. She was evaluated by the endocrinology service and followed up for short stature and hypogonadism. A genetic study was not performed., Conclusions: Rothmund-Thomson syndrome is characterized by atrophy. Only a few cases are reported in the literature. We present two cases of Rothmund-Thomson syndrome, emphasizing its clinical and dermatological characteristics., (Copyright: © 2022 Permanyer.)

Acne is a chronic inflammatory disease of the pilosebaceous unit with multifactorial etiology. Abnormal proliferation of keratinocytes, altered sebum production, inflammation of the sebaceous follicle, and colonization by Cutibacterium acnes have been traditionally implicated. However, the diet has also been highlighted in the pathogenesis because of its direct relation with some biochemical markers and the transcription of specific genes associated with sebaceous gland activity, inflammation, and bacterial proliferation, which together promote the development of the disease, affect the severity of the condition, and modify its response to treatment.

Introducción: El neuroblastoma es el tumor maligno más frecuente en el primer año de vida y el tumor sólido extracraneal más frecuente en la infancia. Solo el 1% de los casos debuta con metástasis cutáneas, caracterizadas por nódulos azulados subcutáneos. Se presenta el caso de un lactante con un neuroblastoma suprarrenal izquierdo en el que las metástasis cutáneas constituían el síntoma principal. Caso clínico: Lactante de sexo femenino, de 2 meses de edad, sin antecedentes de importancia para el padecimiento actual. Acudió por presentar dermatosis diseminada en la región cervical y occipital, el abdomen, el muslo derecho y el pie izquierdo. La dermatosis se caracteriza por nódulos subcutáneos, sólidos, bien delimitados, < 1 cm, de color azulado, que iniciaron su aparición a los 7 días de vida en el hipocondrio derecho, con crecimiento progresivo, asintomáticos. Se realizó biopsia de un nódulo y se reportó la presencia de células pequeñas con núcleo denso hipercromático, escaso citoplasma y dispuestas en nidos. La inmunohistoquímica fue positiva para cromogranina y enolasa neuronal específica. Los hallazgos fueron compatibles con metástasis cutánea de neuroblastoma. Se solicitó valoración y abordaje por oncología pediátrica, que reportó un estadio 4 de la enfermedad y se inició el tratamiento correspondiente. Conclusiones: Los pediatras y los dermatólogos pediatras son los primeros en atender a niños con alguna lesión cutánea. Se deben tener en cuenta las metástasis cutáneas, que pueden aparecer antes o simultáneamente al diagnóstico de un tumor primario. Por lo tanto, se debe realizar un correcto abordaje con el fin de mejorar el pronóstico y la calidad de vida del paciente.

Autism spectrum disorders (ASD) are subdivided into idiopathic (unknown) etiology and secondary, based on known etiology. There are hundreds of causes of ASD and most of them are genetic in origin or related to the interplay of genetic etiology and environmental toxicology. Approximately 30 to 50% of the etiologies can be identified when using a combination of available genetic testing. Many of these gene mutations are either core components of the Wnt signaling pathway or their modulators. The full mutation of the fragile X mental retardation 1 (FMR1) gene leads to fragile X syndrome (FXS), the most common cause of monogenic origin of ASD, accounting for ~ 2% of the cases. There is an overlap of molecular mechanisms in those with idiopathic ASD and those with FXS, an interaction between various signaling pathways is suggested during the development of the autistic brain. This review summarizes the cross talk between neurobiological pathways found in ASD and FXS. These signaling pathways are currently under evaluation to target specific treatments in search of the reversal of the molecular abnormalities found in both idiopathic ASD and FXS.

Background: Leukemia cutis (LC) is the infiltration of neoplastic leukocytes into the skin, causing skin lesions. In children, it appears more frequently in patients with acute myeloblastic leukemia (AML), particularly in subtypes with a monocytic component., Methods: We studied a retrospective cohort including all AML cases from the Hospital Infantil de México Federico Gómez between January 2009 to December 2019 and described the clinical characteristics of those who presented LC and other mucocutaneous manifestations. The information was collected from clinical records and analyzed using SPSS software (version 17)., Results: We identified 54 AML cases: 53.7% were males, and 75.9% of the patients presented at least one dermatosis in the course of the disease. LC was clinically present in 14.8% of patients and was histologically confirmed in 9.2% of them; two congenital leukemia cases were identified. Among these patients, LC was more frequent in males. LC patients were younger than those without LC, the most frequent AML subtype was M2 (37.5%), and the most frequent clinical manifestations were plaques, chloromas, and gingival hyperplasia. None of the patients presented LC before AML diagnosis., Conclusions: Currently, only a few studies about LC on pediatric populations have been reported, and the existing ones have small sample sizes. We found clinical and epidemiological similarities with other populations in the studied sample., (Copyright: © 2021 Permanyer.)

Competing Interests: Competing interest: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest.

[This corrects the article DOI: 10.1371/journal.pmed.1002326.].

Fragile X syndrome (FXS) is caused by a full mutation of the FMR1 gene (>200 CGG repeats and subsequent methylation), such that there is little or no FMR1 protein (FMRP) produced, leading to intellectual disability (ID). Individuals with the premutation allele (55-200 CGG repeats, generally unmethylated) have elevated FMR1 mRNA levels, a consequence of enhanced transcription, resulting in neuronal toxicity and a spectrum of premutation-associated disorders, including the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Here we described 14 patients who had both lowered FMRP and elevated FMR1 mRNA levels, representing dual mechanisms of clinical involvement, which may combine features of both FXS and FXTAS. In addition, the majority of these cases show psychiatric symptoms, including bipolar disorder, and/or psychotic features, which are rarely seen in those with just FXS.

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder seen in older premutation (55-200 CGG repeats) carriers of FMR1. The premutation has excessive levels of FMR1 mRNA that lead to toxicity and mitochondrial dysfunction. The clinical features usually begin in the 60 s with an action or intention tremor followed by cerebellar ataxia, although 20% have only ataxia. MRI features include brain atrophy and white matter disease, especially in the middle cerebellar peduncles, periventricular areas, and splenium of the corpus callosum. Neurocognitive problems include memory and executive function deficits, although 50% of males can develop dementia. Females can be less affected by FXTAS because of a second X chromosome that does not carry the premutation. Approximately 40% of males and 16% of female carriers develop FXTAS. Since the premutation can occur in less than 1 in 200 women and 1 in 400 men, the FXTAS diagnosis should be considered in patients that present with tremor, ataxia, parkinsonian symptoms, neuropathy, and psychiatric problems. If a family history of a fragile X mutation is known, then FMR1 DNA testing is essential in patients with these symptoms.

The aim of the ACE-Obesity Policy study was to assess the economic credentials of a suite of obesity prevention policies across multiple sectors and areas of governance for the Australian setting. The study aimed to place the cost-effectiveness results within a broad decision-making context by providing an assessment of the key considerations for policy implementation. The Assessing Cost-Effectiveness (ACE) approach to priority-setting was used. Systematic literature reviews were undertaken to assess the evidence of intervention effectiveness on body mass index and/or physical activity for selected interventions. A standardised evaluation framework was used to assess the cost-effectiveness of each intervention compared to a 'no intervention' comparator, from a limited societal perspective. A multi-state life table Markov cohort model was used to estimate the long-term health impacts (quantified as health adjusted life years (HALYs)) and health care cost-savings resulting from each intervention. In addition to the technical cost-effectiveness results, qualitative assessments of implementation considerations were undertaken. All 16 interventions evaluated were found to be cost-effective (using a willingness-to-pay threshold of AUD50,000 per HALY gained). Eleven interventions were dominant (health promoting and cost-saving). The incremental cost-effectiveness ratio for the non-dominant interventions ranged from AUD1,728 to 28,703 per HALY gained. Regulatory interventions tended to rank higher on their cost-effectiveness results, driven by lower implementation costs. However, the program-based policy interventions were generally based on higher quality evidence of intervention effectiveness. This comparative analysis of the economic credentials of obesity prevention policies for Australia indicates that there are a broad range of policies that are likely to be cost-effective, although policy options vary in strength of evidence for effectiveness, affordability, feasibility, acceptability to stakeholders, equity impact and sustainability. Implementation of these policies will require sustained co-ordination across jurisdictions and multiple government sectors in order to generate the predicted health benefits for the Australian population., Competing Interests: The authors have declared that no competing interests exist.

It is very common to perform statistical tests to obtain insights about populations based on samples. For instance, in the context of psychology, when a set of instruments are applied to individuals, psychologists typically look for an explanation of particular psychological constructs (variables), such as personality, intelligence, or emotional functioning. It is common to cross statistical information from the results of different psychological tests to measure certain variables or to confirm prior beliefs. Here, we estimate the Joint Probability Density Function of suicide-related vulnerability and protective factors to assess suicide risk in adolescents. A Markov Chain Monte Carlo Method is employed to move away from the typical Gaussian assumption on data. This allows us to estimate probabilities of the development of suicidal ideation based on samples (which form a Markov chain). We employ our proposed statistical method at a high school in Colombia. The results reveal that adolescents can develop suicidal ideation as a consequence of the following factors, together with their corresponding probabilities: poor school performance 52%, low academic expectations 27%, school integration problems 68%, risky eating behaviors (binge-purge) 42%, risky eating behaviors (compensatory measurements) 21%, risky eating habits (restriction) 22%, and low family functionality 16%.

Background: Macrophages show versatile functions in innate immunity, infectious diseases, and progression of cancers and cardiovascular diseases. These versatile functions of macrophages are conducted by different macrophage phenotypes classified as classically activated macrophages and alternatively activated macrophages due to different stimuli in the complex in vivo cytokine environment. Dissecting the regulation of macrophage activations will have a significant impact on disease progression and therapeutic strategy. Mathematical modeling of macrophage activation can improve the understanding of this biological process through quantitative analysis and provide guidance to facilitate future experimental design. However, few results have been reported for a complete model of macrophage activation patterns., Results: We globally searched and reviewed literature for macrophage activation from PubMed databases and screened the published experimental results. Temporal in vitro macrophage cytokine expression profiles from published results were selected to establish Boolean network models for macrophage activation patterns in response to three different stimuli. A combination of modeling methods including clustering, binarization, linear programming (LP), Boolean function determination, and semi-tensor product was applied to establish Boolean networks to quantify three macrophage activation patterns. The structure of the networks was confirmed based on protein-protein-interaction databases, pathway databases, and published experimental results. Computational predictions of the network evolution were compared against real experimental results to validate the effectiveness of the Boolean network models., Conclusion: Three macrophage activation core evolution maps were established based on the Boolean networks using Matlab. Cytokine signatures of macrophage activation patterns were identified, providing a possible determination of macrophage activations using extracellular cytokine measurements.

Objective: To describe potential regional variations in therapies for severe asthma exacerbations in Chilean children and estimate the associated health expenditures., Methods: Observational prospective cohort study in 14 hospitals over a one-year period. Children five years of age or older were eligible for inclusion. Days with oxygen supply and pharmacological treatments received were recorded from the clinical chart. A basic asthma hospitalization basket was defined in order to estimate the average hospitalization cost for a single patient. Six months after discharge, new visits to the Emergency Room (ER), use of systemic corticosteroids and adherence to the controller treatment were evaluated., Results: 396 patients were enrolled. Patients from the public health system and from the north zone received significantly more days of oxygen, systemic corticosteroids and antibiotics. Great heterogeneity in antibiotic use among the participating hospitals was found, from 0 to 92.3% (ICC 0.34, 95% CI 0.16-0.52). The use of aminophylline, magnesium sulfate and ketamine varied from 0 to 36.4% between the different Pediatric Intensive Care Units (ICC 0.353, 95% CI 0.010-0.608). The average cost per inpatient was of $1910 USD. 290 patients (73.2%) completed the follow-up six months after discharge. 76 patients (26.2%) were not receiving any controller treatment and nearly a fourth had new ER visits and use of systemic corticosteroids due to new asthma exacerbations., Conclusions: Considerable practice variation in asthma exacerbations treatment was found among the participating hospitals, highlighting the poor outcome of many patients after hospital discharge, with an important health cost., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: The objective of this study is to examine, from a limited societal perspective, the cost-effectiveness of community-based obesity prevention interventions (CBIs)-defined as a programme of community-level strategies to promote healthy eating and physical activity for Australian children (aged 5-18 years)., Methods: The effectiveness of CBIs was determined by undertaking a literature review and meta-analysis. Commonly implemented strategies to increase physical activity and improve nutrition were costed (in 2010 Australian dollars) to determine the average cost of a generic programme. A multiple cohort Markov model that simulates diseases associated with overweight and obesity was used to estimate the health benefits, measured as health-adjusted life years (HALYs) and healthcare-related cost offsets from diseases averted due to exposure to the intervention. Health and cost outcomes were estimated over the lifetime of the target population. Monte-Carlo simulation was used to assess second-order uncertainty of input parameters to estimate mean incremental cost-effectiveness ratios (ICER) with 95% uncertainty intervals (UIs). Scenario analyses tested variations in programme intensity, target population, and duration of effect., Results: The meta-analysis revealed a small but significant difference in BMI z-score (mean difference of - 0.07 (95% UI: - 0.13 to - 0.01)) favouring the CBI community compared with the control. The estimated net cost of implementing CBIs across all local government areas (LGAs) in Australia was AUD426M (95% UI: AUD3M to AUD823M) over 3 years. This resulted in 51,792 HALYs gained (95% UI: 6816 to 96,972) over the lifetime of the cohort. The mean ICER was AUD8155 per HALY gained (95% UI: AUD237 to AUD81,021), with a 95% probability of being cost-effective at a willingness to pay threshold of AUD50,000 per HALY., Conclusions: CBIs are cost-effective obesity prevention initiatives; however, implementation across Australia will be (relatively) expensive when compared with current investments in preventive health.

Introduction: There is a high rate of deliveries in adolescents in Mexico. This age group is vulnerable to obstetric complications, including lacerations of the anal sphincter., Objective: To determine the prevalence of third and fourth degree perineal tears in adolescents during childbirth, and to evaluate risk factors in comparison with deliveries with lacerations of adult women., Methods: All obstetric care episodes were reviewed from a public tertiary hospital data in Monterrey, Mexico in 2014. Age, primiparity, delivery instrumentation, episiotomy, body mass index, product weight and tear´s degree were documented at the deliveries with tears of third and fourth degree., Results: The prevalence of third and fourth degree tears of 2.0% was found in the general population, being adolescents the most affected with 2.5%. The unadjusted odds ratio of high-grade tears in adolescent females at delivery, compared to adult females, was 1.36 (95% CI = 0.99-1.86, p = 0.05). No difference was found when comparing risk factors among high-grade tear deliveries in adolescents versus adults., Conclusions: A higher prevalence than previous reported for high grade tears during delivery was found. The data suggest adolescence as a risk factor for high-grade tears during delivery., Competing Interests: Conflict of interest: nothing

Background: Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this., Objective: Describe clinical characteristics of children hospitalized for asthma exacerbation., Methods: Observational prospective cohort study in 14 hospitals. Over a one-year period, children five years of age or older hospitalized with asthma exacerbation were eligible for inclusion. Parents completed an online questionnaire with questions on demographic information, about asthma, indoor environmental contaminant exposure, comorbidities and beliefs about disease and treatment. Disease control was assessed by the Asthma Control Test. Inhalation technique was observed using a checklist., Results: 396 patients were enrolled. 168 children did not have an established diagnosis of asthma. Only 188 used at least one controller treatment at the time of hospitalization. 208 parents said they believed their child had asthma only when they had an exacerbation and 97 correctly identified inhaled corticosteroids as anti-inflammatory treatment. 342 patients used the wrong spacer and 73 correctly performed all steps of the checklist., Conclusions: Almost half of the patients were not diagnosed with asthma at the time of hospitalization despite having a medical history suggestive of the disease. In the remaining patients with an established diagnosis of asthma potentially modifiable factors like bad adherence to treatment and poor inhalation technique were found. Implementing a nationwide asthma program including continued medical education for the correct diagnosis and follow up of these patients and asthma education for patients and caregivers is needed to reduce asthma hospitalization rates in Chilean children., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

The authors have requested that the following changes be made to their paper [...]., Competing Interests: The authors declare no conflict of interest.

The Health Star Rating (HSR) system is a voluntary front-of-pack labelling (FoPL) initiative endorsed by the Australian government in 2014. This study examines the impact of the HSR system on pre-packaged food reformulation measured by changes in energy density between products with and without HSR. The cost-effectiveness of the HSR system was modelled using a proportional multi-state life table Markov model for the 2010 Australian population. We evaluated scenarios in which the HSR system was implemented on a voluntary and mandatory basis (i.e., HSR uptake across 6.7% and 100% of applicable products, respectively). The main outcomes were health-adjusted life years (HALYs), net costs, and incremental cost-effectiveness ratios (ICERs). These were calculated with accompanying 95% uncertainty intervals (95% UI). The model predicted that HSR-attributable reformulation leads to small changes [corrected] in mean population energy intake (voluntary: -0.98 kJ/day; mandatory: -11.81 kJ/day). [corrected]. These are likely to result in changes in mean body weight (voluntary: -0.01 kg [95% UI: -0.012 to -0.006]; mandatory: -0.11 kg [95% UI: -0.14 to -0.07, and HALYs gained [corrected] (voluntary: 4207 HALYs gained [corrected] [95% UI: 2438 to 6081]; mandatory: 49,949 HALYs gained [95% UI: 29,291 to 72,153]). The HSR system [corrected] could be considered cost-effective relative to a willingness-to-pay threshold of A$50,000 per HALY (incremental cost effectiveness ratio for voluntary: [corrected] A$1728 per HALY [95% UI: dominant to 10,445] and mandatory: A$4752 per HALY [95% UI: dominant to 16,236]).

The aim of this paper is to study the behavior of an earth fill dam, analyzing the deformations determined by high precision geodetic techniques and those obtained by the Finite Element Method (FEM). A large number of control points were established around the area of the dam, and the measurements of their displacements took place during several periods. In this study, high-precision leveling and GNSS (Global Navigation Satellite System) techniques were used to monitor vertical and horizontal displacements respectively. Seven surveys were carried out: February and July 2008, March and July 2013, August 2014, September 2015 and September 2016. Deformations were predicted, taking into account the general characteristics of an earth fill dam. A comparative evaluation of the results derived from predicted (FEM) and observed deformations shows the differences on average being 20 cm for vertical displacements, and 6 cm for horizontal displacements at the crest. These differences are probably due to the simplifications assumed during the FEM modeling process: critical sections are considered homogeneous along their longitude, and the properties of the materials were established according to the general characteristics of an earth fill dam. These characteristics were taken from the normative and similar studies in the country. This could also be due to the geodetic control points being anchored in the superficial layer of the slope when the construction of the dam was finished.

Background: A sugar-sweetened beverage (SSB) tax in Mexico has been effective in reducing consumption of SSBs, with larger decreases for low-income households. The health and financial effects across socioeconomic groups are important considerations for policy-makers. From a societal perspective, we assessed the potential cost-effectiveness, health gains, and financial impacts by socioeconomic position (SEP) of a 20% SSB tax for Australia., Methods and Findings: Australia-specific price elasticities were used to predict decreases in SSB consumption for each Socio-Economic Indexes for Areas (SEIFA) quintile. Changes in body mass index (BMI) were based on SSB consumption, BMI from the Australian Health Survey 2011-12, and energy balance equations. Markov cohort models were used to estimate the health impact for the Australian population, taking into account obesity-related diseases. Health-adjusted life years (HALYs) gained, healthcare costs saved, and out-of-pocket costs were estimated for each SEIFA quintile. Loss of economic welfare was calculated as the amount of deadweight loss in excess of taxation revenue. A 20% SSB tax would lead to HALY gains of 175,300 (95% CI: 68,700; 277,800) and healthcare cost savings of AU$1,733 million (m) (95% CI: $650m; $2,744m) over the lifetime of the population, with 49.5% of the total health gains accruing to the 2 lowest quintiles. We estimated the increase in annual expenditure on SSBs to be AU$35.40/capita (0.54% of expenditure on food and non-alcoholic drinks) in the lowest SEIFA quintile, a difference of AU$3.80/capita (0.32%) compared to the highest quintile. Annual tax revenue was estimated at AU$642.9m (95% CI: $348.2m; $1,117.2m). The main limitations of this study, as with all simulation models, is that the results represent only the best estimate of a potential effect in the absence of stronger direct evidence., Conclusions: This study demonstrates that from a 20% tax on SSBs, the most HALYs gained and healthcare costs saved would accrue to the most disadvantaged quintiles in Australia. Whilst those in more disadvantaged areas would pay more SSB tax, the difference between areas is small. The equity of the tax could be further improved if the tax revenue were used to fund initiatives benefiting those with greater disadvantage.

Background: Reducing automobile dependence and improving rates of active transport may reduce the impact of obesogenic environments, thereby decreasing population prevalence of obesity and other diseases where physical inactivity is a risk factor. Increasing the relative cost of driving by an increase in fuel taxation may therefore be a promising public health intervention for obesity prevention., Methods: A scoping review of the evidence for obesity or physical activity effect of changes in fuel price or taxation was undertaken. Potential health benefits of an increase in fuel excise taxation in Australia were quantified using Markov modelling to simulate obesity, injury and physical activity related health impacts of a fuel excise taxation intervention for the 2010 Australian population. Health adjusted life years (HALYs) gained and healthcare cost savings from diseases averted were estimated. Incremental cost-effectiveness ratios (ICERs) were reported and results were tested through sensitivity analysis., Results: Limited evidence on the effect of policies such as fuel taxation on health-related behaviours currently exists. Only three studies were identified reporting associations between fuel price or taxation and obesity, whilst nine studies reported associations specifically with physical activity, walking or cycling. Estimates of the cross price elasticity of demand for public transport with respect to fuel price vary, with limited consensus within the literature on a probable range for the Australian context. Cost-effectiveness modelling of a AUD0.10 per litre increase in fuel excise taxation using a conservative estimate of cross price elasticity for public transport suggests that the intervention would be cost-effective from a limited societal perspective (237 HALYs gained, AUD2.6 M in healthcare cost savings), measured against a comparator of no additional increase in fuel excise. Under "best case" assumptions, the intervention would be more cost-effective (3181 HALYs gained, AUD34.2 M in healthcare cost savings)., Conclusions: Exploratory analysis suggests that an intervention to increase fuel excise taxation may deliver obesity and physical activity related benefits. Whilst such an intervention has significant potential for cost-effectiveness, potential equity and acceptability impacts would need to be minimised. A better understanding of the effectiveness and cost-effectiveness of a range of transport interventions is required in order to achieve more physically active transport environments.

Background: Studies consistently find that supportive neighbourhood built environments increase physical activity by encouraging walking and cycling. However, evidence on the cost-effectiveness of investing in built environment interventions as a means of promoting physical activity is lacking. In this study, we assess the cost-effectiveness of increasing sidewalk availability as one means of encouraging walking., Methods: Using data from the RESIDE study in Perth, Australia, we modelled the cost impact and change in health-adjusted life years (HALYs) of installing additional sidewalks in established neighbourhoods. Estimates of the relationship between sidewalk availability and walking were taken from a previous study. Multistate life table models were used to estimate HALYs associated with changes in walking frequency and duration. Sensitivity analyses were used to explore the impact of variations in population density, discount rates, sidewalk costs and the inclusion of unrelated healthcare costs in added life years., Results: Installing and maintaining an additional 10 km of sidewalk in an average neighbourhood with 19 000 adult residents was estimated to cost A$4.2 million over 30 years and gain 24 HALYs over the lifetime of an average neighbourhood adult resident population. The incremental cost-effectiveness ratio was A$176 000/HALY. However, sensitivity results indicated that increasing population densities improves cost-effectiveness., Conclusions: In low-density cities such as in Australia, installing sidewalks in established neighbourhoods as a single intervention is unlikely to cost-effectively improve health. Sidewalks must be considered alongside other complementary elements of walkability, such as density, land use mix and street connectivity. Population density is particularly important because at higher densities, more residents are exposed and this improves the cost-effectiveness. Health gain is one of many benefits of enhancing neighbourhood walkability and future studies might consider a more comprehensive assessment of its social value (eg, social cohesion, safety and air quality)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Vitronectin, a multifunctional glycoprotein, is involved in coagulation, inhibition of the formation of the membrane attack complex (MAC), cell adhesion and migration, wound healing, and tissue remodeling. The primary cellular source of vitronectin is hepatocytes; it is not known whether resident cells of airways produce vitronectin, even though the glycoprotein has been found in exhaled breath condensate and bronchoalveolar lavage from healthy subjects and patients with interstitial lung disease. It is also not known whether vitronectin expression is altered in subjects with asthma and COPD. In this study, bronchial tissue from 7 asthmatic, 10 COPD and 14 control subjects was obtained at autopsy and analyzed by immunohistochemistry to determine the percent area of submucosal glands occupied by vitronectin. In a separate set of experiments, quantitative colocalization analysis was performed on tracheobronchial tissue sections obtained from donor lungs (6 asthmatics, 4 COPD and 7 controls). Vitronectin RNA and protein expressions in bronchial surface epithelium were examined in 12 subjects who undertook diagnostic bronchoscopy. Vitronectin was found in the tracheobronchial epithelium from asthmatic, COPD, and control subjects, although its expression was significantly lower in the asthmatic group. Colocalization analysis of 3D confocal images indicates that vitronectin is expressed in the glandular serous epithelial cells and in respiratory surface epithelial cells other than goblet cells. Expression of the 65-kDa vitronectin isoform was lower in bronchial surface epithelium from the diseased subjects. The cause for the decreased vitronectin expression in asthma is not clear, however, the reduced concentration of vitronectin in the epithelial/submucosal layer of airways may be linked to airway remodeling.

Genital malformations occur at a high frequency in humans, affecting ~1:250 live births. The molecular mechanisms of external genital development are beginning to be identified; however, the origin of cells that give rise to external genitalia is unknown. Here we use cell lineage analysis to show that the genital tubercle, the precursor of the penis and clitoris, arises from two populations of progenitor cells that originate at the lateral edges of the embryo, at the level of the posterior hindlimb buds and anterior tail. During body wall closure, the left and right external genital progenitor pools are brought together at the ventral midline, where they form the paired genital swellings that give rise to the genital tubercle. Unexpectedly, the left and right external genital progenitor pools form two lineage-restricted compartments in the phallus. Together with previous lineage studies of limb buds, our results indicate that, at the pelvic level, the early lateral mesoderm is regionalized from medial to lateral into dorsal limb, ventral limb, and external genital progenitor fields. These findings have implications for the evolutionary diversification of external genitalia and for the association between external genital defects and disruption of body wall closure, as seen in the epispadias-extrophy complex.

Myosin molecules from smooth muscle and non-muscle cells are known to self-assemble into side-polar filaments in vitro. However, the in situ mechanism of filament assembly is not clear and the question of whether there is a unique length for myosin filaments in smooth muscle is still under debate. In this study we measured the lengths of 16,587 myosin filaments in three types of smooth muscle cells using serial electron microscopy (EM). Sheep airway and pulmonary arterial smooth muscle as well as rabbit carotid arterial smooth muscle were fixed for EM and serial ultra-thin (50-60 nm) sections were obtained. Myosin filaments were traced in consecutive sections to determine their lengths. The results indicate that there is not a single length for the myosin filaments; instead there is a wide variation in lengths. The plots of observation frequency versus myosin filament length follow an exponential decay pattern. Analysis suggests that in situ assembly of myosin filaments in smooth muscle is governed by random processes of linear polymerization and de-polymerization, and that the dynamic equilibrium of these processes determines the observed length distribution.

Introduction: Iron depleted deposits are the first link in the chain of events leading to iron deficiency which is the most prevalent nutritional shortage and main cause of anemia worldwide. This situation can be prevented through food fortification., Objective: To compare the efficacy of amino acid chelate iron with ferrous sulfate as fortifier of a dietary complement in preschoolers with iron deficiency., Materials and Methods: This study was a blinded clinical trial with randomized groups. We analyzed 56 preschoolers with iron deficiency (ferritin < 24 ng/ml) that received 13 g of milk with 12.5 mg of iron, either amino acid chelate or in the ferrous sulfate form. After two months, hemoglobin, hematocrit and serum ferritin concentrations were measured., Results: In the ferrous sulfate group, ferritin concentration increased from 18.8 ng/ml to 24.1 ng/ml, while the variation was of 18.4 ng/ml to 29.7 ng/ml in the amino acid chelate group, with statistically differences in both cases. Serum ferritin was different between groups, being higher in iron amino acid chelate group (p=0.022). Hemoglobin and hematocrit levels did not change after the intervention. Adverse reactions in the ferrous sulfate group were 35.7%, compared with 42.9% in the iron amino acid chelate group; 5 children had respiratory tract infection, without statistical differences., Conclusions: Both compounds increased serum ferritin concentration, with a higher increase in those who were given milk with iron amino acid chelate. There were no differences in the adverse reactions and infections incidences between the groups.

Background: One of the most puzzling events in evolution is the reduction and loss of the phallus in birds. All birds reproduce by internal fertilization, but only ∼3% of birds have retained a phallus capable of intromission. A number of hypotheses have been proposed for the evolutionary mechanisms that drove phallus reduction; however, the underlying developmental mechanisms are unknown., Results: We investigated genital development in two sister clades of birds, Galliformes (land fowl), most of which lack an intromittent phallus, and Anseriformes (waterfowl), which have well developed phalluses; and in two outgroups, Paleognathae (emus) and Crocodilia (alligators). Galliform embryos undergo cryptic development of a genital tubercle, the precursor of the phallus, but this later undergoes apoptosis, leading to regression of the tubercle. At the molecular level, a derived pattern of Bmp4 expression was identified in chick (a galliform) genital tubercles. Inhibition of Bmp signaling in chick genitalia rescues cells from apoptosis and prevents phallus regression, whereas activation of Bmp signaling in duck (an anseriform) genitalia induces a galliform-like pattern of apoptosis. Thus, distal Bmp activity is necessary and sufficient to induce apoptosis in Galloanserae genital tubercles., Conclusions: Our results indicate that evolutionary reduction of the intromittent phallus in galliform birds occurred not by disruption of outgrowth signals but by de novo activation of cell death by Bmp4 in the genital tubercle. These findings, together with discoveries implicating Bmps in evolution of beak shape, feathers, and toothlessness, suggest that modulation of Bmp gene regulation played a major role in the evolution of avian morphology., (Copyright © 2013 Elsevier Ltd. All rights reserved.)