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A theoretical and practical distinction is drawn between sex offenders and consumers of child pornography on the bases of their unique and different psychological makeups and motives to offend. Distinct psychological profiles have been revealed in clinical practice and in research between “active” sex offenders (e.g., sexual assault, sexual abuse, molestation, active pedophiles, etc.) and “passive” sex offenders (i.e., those prosecuted for consumption of child pornography). Recommendations are made for legislation changes and development of treatment approaches, based on these differences.

Purpose To investigate whether low complement levels can predict worse outcomes in patients hospitalized with positive anti-phospholipid antibodies. Methods This was a retrospective cohort study. We obtained demographics, laboratory, and prognostic data of all consecutive patients hospitalized between 2007 and 2021, for whatever reason, with at least one positively abnormal anti-phospholipid antibody, who were also tested for complement levels (C3 or C4). We then compared the rates of long-term mortality, 1-year mortality, deep vein thrombosis, and pulmonary emboli between groups of low complement and normal complement levels. Multivariate analysis was used to control for levels of clinical and laboratory confounders. Results We identified 32,286 patients tested for anti-phospholipid antibodies. Of those patients, 6800 tested positive for at least one anti-phospholipid antibody and had a documented complement level. Significant higher mortality rates were found in the low complement group, with an odds ratio for mortality (OR 1.93 CI 1.63–2.27 p < .001). Deep vein thrombosis and pulmonary emboli rates were similar. Multivariate analysis confirmed that low complement was an independent predictor for mortality after controlling for age, sex, dyslipidemia, chronic heart failure (CHF), chronic kidney disease (CKD), and anemia. Conclusions Our study results indicate that low complement is associated with significantly higher mortality rates in admitted patients with elevated levels of anti-phospholipid antibodies. This finding correlates with recent literature suggesting a vital role for complement activation in anti-phospholipid syndrome.

The possibility of processing low-cost types of biomass, including sawdust, into oxygen-free hydrocarbon fuel was studied. Synthesis of liquid fuel was performed by slow pyrolysis of plant raw materials under pressure. It was revealed that the resulting liquid fuel had a higher volatility than the feedstock and an increased fuel calorific power compared to conventional biofuels, which was explained by deoxygenation. The possibility of producing oxygen-free liquid fuel from vegetable raw material was substantiated. It was proposed to use produced oxygen-free liquid fuels instead of mineral fuels for sustainable development.

In Escherichia coli, replication of both strands of genomic DNA is carried out by a single replicase—DNA polymerase III holoenzyme (pol III HE). However, in certain genetic backgrounds, the low-fidelity TLS polymerase, DNA polymerase V (pol V) gains access to undamaged genomic DNA where it promotes elevated levels of spontaneous mutagenesis preferentially on the lagging strand. We employed active site mutants of pol III (pol IIIα_S759N) and pol V (pol V_Y11A) to analyze ribonucleotide incorporation and removal from the E. coli chromosome on a genome-wide scale under conditions of normal replication, as well as SOS induction. Using a variety of methods tuned to the specific properties of these polymerases (analysis of lacI mutational spectra, lacZ reversion assay, HydEn-seq, alkaline gel electrophoresis), we present evidence that repair of ribonucleotides from both DNA strands in E. coli is unequal. While RNase HII plays a primary role in leading-strand Ribonucleotide Excision Repair (RER), the lagging strand is subject to other repair systems (RNase HI and under conditions of SOS activation also Nucleotide Excision Repair). Importantly, we suggest that RNase HI activity can also influence the repair of single ribonucleotides incorporated by the replicase pol III HE into the lagging strand.

Resumen Introducción La infección periprotésica (IPP) es una de las complicaciones más serias en una artroplastia total de rodilla (ATR). Pese a esto, existe poca literatura chilena respecto de esta patología. Objetivos Determinar la incidencia, las comorbilidades, los microorganismos aislados y su susceptibilidad antibiótica, y la morbimortalidad en pacientes con IPP. Materiales y Métodos Estudio descriptivo y retrospectivo en pacientes operados entre 2001 y 2020 por gonartrosis, con una ATR primaria, en un mismo centro de salud, con al menos 1 año de seguimiento. Se excluyeron pacientes operados en otros centros o con registros clínicos incompletos. Se registraron las comorbilidades, los microorganismos aislados, la susceptibilidad antibiótica, y la sobrevida por medio de una búsqueda sistemática de las fichas clínicas de los pacientes con IPP. Se utilizó estadística descriptiva para presentar los datos. Resultados Se incluyeron 544 ATRs, de las cuales 8 (1,47%) presentaron IPP, y los pacientes tenían una edad promedio de presentación de 66 (±5,7) años, e índice de masa corporal (IMC) promedio de 30,3 (±4,5) kg/m2. La mediana de tiempo de presentación de la IPP fue de 411 (±1.034) días. Las principales comorbilidades registradas fueron hipertensión arterial en 5 (62,5%), tabaquismo en 4 (50%) casos, y dislipidemia in 4 (50%) casos. En total, 5 (62,5%) pacientes presentaron etiología polimicrobiana, y en 3 (37,5%) se aisló un solo microorganismo. Los principales agentes aislados fueron Staphylococcus aureus y Staphylococcus coagulasa negativo, ambos multirresistentes, en 6 (75%) y 3 (37,5%) pacientes respectivamente. Todos los pacientes recibieron tres dosis de cefazolina como profilaxis quirúrgica. Se describe una sensibilidad del 100% frente a vancomicina y rifampicina (12/12 cultivos), y una resistencia del 83,4% al ciprofloxacino (4/9 cultivos). Un total de 2 (25%) pacientes fallecieron después de 3 años de la ATR por causas no relacionadas con la IPP. No hubo casos de recidiva infecciosa tras la revisión. Conclusión Se encontró una incidencia de 1,47% (8 casos) de IPP. Todos los pacientes con IPP presentaron alguna comorbilidad prequirúrgica. Los principales agentes microbiológicos identificados fueron multirresistentes y susceptibles a vancomicina y rifampicina.

Background Electroconvulsive therapy (ECT) is a procedural treatment that is potentially life-saving for some patients with severe psychiatric illness. At the start of the global coronavirus disease 2019 (COVID-19) pandemic, ECT practice was remarkably disrupted, putting vulnerable individuals at increased risk of symptom exacerbation and death by suicide. This study aimed to capture the self-reported experiences of psychiatrists based at healthcare facilities across Canadian provinces who were delivering ECT treatments during the first phase of the COVID-19 pandemic (i.e., from mid-March 2020 to mid-May 2020). Methods A multidisciplinary team of experts developed a survey focusing on five domains: ECT unit operations, decision-making, hospital resources, ECT procedure, and mitigating patient impact. Responses were collected from psychiatrists providing ECT at 67 ECT centres in Canada, grouped by four geographical regions (Ontario, Quebec, Atlantic Canada, and Western Canada). Results Clinical operations of ECT programs were disrupted across all four regions – however, centres in Atlantic Canada were able to best preserve outpatient and maintenance care, while centres in Western Canada were able to best preserve inpatient and acute care. Similarly, Atlantic and Western Canada demonstrated the best decision-making practices of involving the ECT team and clinical ethicists in the development of pandemic-related guidelines. Across all four regions, ECT practice was affected by the redeployment of professionals, the shortage of personal protective equipment, and the need to enforce social distancing. Attempts to introduce modifications to the ECT delivery room and minimize bag-valve-mask ventilation were consistently reported. All four regions developed a new patient prioritization framework, and Western Canada, notably, aimed to provide ECT to only the most severe cases. Conclusions The results suggest that ECT provision was disproportionately affected across different parts of Canada. Possible factors that could explain these interregional differences include population, distribution of urban vs. rural areas, pre-pandemic barriers in access to ECT, number of cases, ability to control the spread of infection, and the general reduction in physicians’ activities across different areas of health care. Studying these factors in the future will inform how medical centres should respond to public health emergencies and pandemic-related circumstances in the context of procedural treatments.

PURPOSE Selumetinib can increase radioactive iodine (RAI) avidity in RAI-refractory tumors. We investigated whether selumetinib plus adjuvant RAI improves complete remission (CR) rates in patients with differentiated thyroid cancer (DTC) at high risk of primary treatment failure versus RAI alone. METHODS ASTRA (ClinicalTrials.gov identifier: NCT01843062 ) is an international, phase III, randomized, placebo-controlled, double-blind trial. Patients with DTC at high risk of primary treatment failure (primary tumor > 4 cm; gross extrathyroidal extension outside the thyroid gland [T4 disease]; or N1a/N1b disease with ≥ 1 metastatic lymph node(s) ≥ 1 cm or ≥ 5 lymph nodes [any size]) were randomly assigned 2:1 to selumetinib 75 mg orally twice daily or placebo for approximately 5 weeks (no stratification). On treatment days 29-31, recombinant human thyroid-stimulating hormone (0.9 mg)–stimulated RAI (131I; 100 mCi/3.7 GBq) was administered, followed by 5 days of selumetinib/placebo. The primary end point (CR rate 18 months after RAI) was assessed in the intention-to-treat population. RESULTS Four hundred patients were enrolled (August 27, 2013-March 23, 2016) and 233 randomly assigned (selumetinib, n = 155 [67%]; placebo, n = 78 [33%]). No statistically significant difference in CR rate 18 months after RAI was observed (selumetinib n = 62 [40%]; placebo n = 30 [38%]; odds ratio 1.07 [95% CI, 0.61 to 1.87]; P = .8205). Treatment-related grade ≥ 3 adverse events were reported in 25/154 patients (16%) with selumetinib and none with placebo. The most common adverse event with selumetinib was dermatitis acneiform (n = 11 [7%]). No treatment-related deaths were reported. CONCLUSION Postoperative pathologic risk stratification identified patients with DTC at high risk of primary treatment failure, although the addition of selumetinib to adjuvant RAI failed to improve the CR rate for these patients. Future strategies should focus on tumor genotype–tailored drug selection and maintaining drug dosing to optimize RAI efficacy.

To date, there are numerous studies on the effect of COVID-19 on the course of autoimmune rheumatic diseases and the value of vaccination in preventing this dangerous viral infection.Objective: to assess the effect of coronavirus infection on the course of rheumatoid arthritis (RA), the severity of infection, the effect of current baseline therapy on infection outcomes, and the role of vaccination against COVID-19.Patients and methods. 134 patients with a reliable diagnosis of RA were interviewed and their outpatient records analysed during the pandemic period from January 2020 to July 2021.Results. Most of the patients were in the older age group (62.7 years on average), had an average disease duration of 13 years, low to moderate RA activity, comorbidities including arterial hypertension, excess body weight, type 2 diabetes mellitus, etc. All patients received synthetic basic anti-inflammatory drugs (BАID) and glucocorticoids (GC). Thirtyseven (27.6%) patients were vaccinated with the Sputnik V vaccine. Their adverse events were represented by soreness at the injection site (n=6) and transient flu-like syndrome (n=6). Worsening of joint syndrome was reported by 1 patient. COVID-19 was suffered by 43 patients, none of whom were vaccinated. 7 patients were hospitalized, 3 patients died (all had severe comorbidities). In the post-infection period, weakness (64%), memory impairment (48.7%), reduced ability to work (38.5%) persisted for a long time (42 days on average), which was due to the long withdrawal of BАID.Conclusion. No exacerbations of the disease were noted in those vaccinated with Sputnik V. COVID-19 was detected in 43 (32.1%) patients, 7 of whom required hospitalization and 3 died. Exacerbation of RA in the post-infection period was associated with prolonged withdrawal of BАID.

The article aims to develop an integrated method for managing an industrial enterprise highly responsive to the challenges of a changing environment. The theory of the firm, the general theory of management and strategic management theory constitute the methodological basis of the study. The research methods are structural-logical analysis, comparative analysis, and matrixing. We distinguish between three industrial enterprise management methods, based on: (a) complex financial indicators, (b) a balanced scorecard, and (c) a system of continuous improvements. The results of comparative analysis allowed identifying high-potential methods of strategic management. We conclude that it is expedient to integrate various methods, which will level the shortcomings of each of them and, in some cases, help obtain a synergistic effect. The study proposes a mechanism for integrating a balanced scorecard with the Hoshin Kanri tools, which contributes to the development of strategic management theory. The mechanism can be of use for industrial enterprises when formulating their development strategy.

Microbial communities participate in many essential processes from biogeochemical cycles to the maintenance of human health. The structure and functions of these communities are dynamic properties that depend on poorly understood interactions among different species.

XLSX file - 108K, Primary tumor group statistics.

XLSX file - 33K, List of primary antibodies used to probe RPMA slides.

XLSX file - 351K, Spearman's Rho correlation analysis results for the short-survivor group, using RPMA data.

XLSX file - 242K, Spearman's Rho correlation analysis results for the entire study set, using RPMA data.

Purpose: There is an urgent need for therapies that will reduce the mortality of patients with bone metastasis. In this study, we profiled the protein signal pathway networks of the human bone metastasis microenvironment. The goal was to identify sets of interacting proteins that correlate with survival time following the first diagnosis of bone metastasis.Experimental Design: Using Reverse Phase Protein Microarray technology, we measured the expression of 88 end points in the bone microenvironment of 159 bone metastasis tissue samples derived from patients with primary carcinomas and sarcomas.Results: Metastases originating from different primary tumors showed similar levels of cell signaling across tissue types for the majority of proteins analyzed, suggesting that the bone microenvironment strongly influences the metastatic tumor signaling profiles. In a training set (72 samples), TNF receptor 1, alone (P = 0.0013) or combined with serotonin (P = 0.0004), TNFα (P = 0.0214), and RANK (P = 0.0226), was associated with poor survival, regardless of the primary tumor of origin. Results were confirmed by (i) analysis of an independent validation set (71 samples) and (ii) independent bioinformatic analysis using a support vector machine learning model. Spearman rho analysis revealed a highly significant number of interactions intersecting with ERα S118, serotonin, TNFα, RANKL, and matrix metalloproteinase in the bone metastasis signaling network, regardless of the primary tumor. The interaction network pattern was significantly different in the short versus long survivors.Conclusions: TNF receptor 1 and neuroendocrine-regulated protein signal pathways seem to play an important role in bone metastasis and may constitute a novel drug-targetable mechanism of seed-soil cross talk in bone metastasis. Clin Cancer Res; 19(9); 2473–85. ©2013 AACR.

PDF file - 58K, Machine learning dataset characteristics.

XLSX file - 60K, Bone metastasis specimen study set.

PDF file - 3431K, Anti-TNFR1 antibody validation by western blot. Area Under the Curve (AUC) value changes with the data set size in the machine learning model. Anti-Serotonin antibody validation by competition assay using reverse phase protein microarray (RPMA).

XLSX file - 350K, Spearman's Rho correlation analysis results for the long-survivor group, using RPMA data.

Desenvolvido pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM), o Guia Prático em Doenças da Tireoide está integrado ao rol de materiais de divulgação científica e educação médica lançados pela instituição nos últimos anos. Em 28 capítulos elaborados por professores, pesquisadores e endocrinologistas com reconhecimento mundial e larga experiência clínica, o guia contempla tópicos que se estendem da fisiologia tireoidiana à abordagem diagnóstica e terapêutica dos pacientes com as mais diversas doenças da tireoide. A confiabilidade dos dados compilados e o sólido conhecimento de seus colaboradores condicionam este livro como auxílio essencial para consulta durante o atendimento dos pacientes em consultórios, ambulatórios ou enfermarias, além de oportunidade única de atualização a estudantes, médicos residentes e profissionais com particular interesse na Tireoidologia.

Resumen Introducción El error técnico más común durante la reconstrucción del ligamento cruzado anterior (LCA) es la ubicación incorrecta del túnel. Es incierto si un túnel tibial mal ubicado puede corregirse en el intraoperatorio. Objetivo Medir el desplazamiento del injerto de tejido blando con tornillos de interferencia tibial. Materiales y métodos Estudio experimental ex vivo en 28 rodillas porcinas. Se cosechó el tendón flexor de la extremidad posterior, que fue duplicado y dimensionado para que pasara a través de un túnel tibial mal posicionado. Las muestras se dividieron en 4 grupos según el cuadrante de entrada (anterior [A], posterior [P], medial [M], o lateral [L]) de un tornillo de interferencia tibial de 9 mm con relación al injerto. Se ubicó una regla milimétrica en la meseta tibial, la cual fue fotografiada con una cámara EOS T6 (Canon Inc., Ōta, Tokio, Japón), y la imagen fue digitalizada, y puesta en escala a tamaño. La distancia y dirección de los desplazamientos del injerto se midieron con Adobe Photoshop CC 2019 (San José, CA, EEUU). Se analizaron las diferencias medias entre los grupos por análisis de la varianza (analysis of variance, ANOVA, en inglés) unidireccional. El análisis estadístico se realizó con el programa Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Armonk, NY, EEUU), versión 25.0 (p ≤ 0,05)). Resultados La distancias medias de los desplazamientos del injerto fueron similares en todos los grupos: A – 4,4 mm; P – 4,6 mm; M – 4,5 mm; y L – 4,3 mm, sin diferencias estadísticamente significativas (p = 0,894). Las direcciones medias de los desplazamientos del injerto también fueron similares entre los 4 grupos: A – 176° (desviación estándar [DE]: ± 15,4°); P – 165° (DE: ± 16,6°); M – 166° (DE: ± 12,1°); y L – 169° (DE: ± 10,6°). No se encontraron diferencias estadísticamente significativas (p = 0.42). Conclusiones Independientemente del cuadrante de entrada, se observó un desplazamiento constante del injerto hacia el lado opuesto cuando el tornillo tibial alcanzaba la superficie articular. Relevancia clínica: el tornillo tibial mal posicionado puede corregirse en el intraoperatorio con fijación proximal en cuadrante específico, y debe alcanzar la superficie articular para generar un desplazamiento efectivo del injerto. Sin embargo, no podemos predecir la magnitud de error en todos los túneles mal brocados, que debe ser evaluada caso a caso.

Hematidrosis is a rare disease. Isolated cases are described in the literature, which makes it impossible to study the etiology and pathogenesis of the disease. The most convincing are the assumptions about the role of emotional stress in the clinical manifestations of the disease. The author presents his own 2-year observation of a girl who periodically had bleeding from the nose and ear canal.

The innovative technology of sulphurous-alkaline waste recycling after sulfur removal to produce technogenic soil was proposed and tested. The ecological safety of the obtained granular product was proven. Product granulometric composition, its density, humidity and compactibility vs. natural soils were researched. Applicability of obtained material as technogenic soil was substantiated. High strength properties of obtained technogenic soil were identified for enabling steep slope fillings and reducing the earthwork area.

AAC Oravena is a white-hulled spring oat (Avena sativa L.) cultivar selected and developed under organic management. AAC Oravena yields well under organic and conventional production systems, compared with check cultivars. AAC Oravena has good milling quality. AAC Oravena was registered (Reg. No. 7561) by the Variety Registration Office, Canada Food Inspection Agency, on 3 July 2014.

Plant viruses cause systemic diseases that severely impair plant growth and development. While the accumulation of viruses in the root system has long been established, little is known as to how viruses affect root architecture. Here, we examined how the emerging tobamovirus, tomato brown rugose fruit virus (ToBRFV), alters root development in tomato. We found that ToBRFV and tobacco mosaic virus both invaded root systems during the first week of infection. ToBRFV infection of tomato plants resulted in a significant decrease in root biomass and elongation and root-to-shoot ratio and a marked suppression of root branching. Mutation in RNA-dependent RNA polymerase 6 increased the susceptibility of tomato plants to ToBRFV, resulting in severe reduction of various root growth parameters including root branching. Viral root symptoms were associated with the accumulation of auxin response factor 10a (SlARF10a) transcript, a homolog of Arabidopsis ARF10, a known suppressor of lateral root development. Interestingly, loss-of-function mutation in SlARF10a moderated the effect of ToBRFV on root branching. In contrast, downregulation of sly-miR160a, which targets SlARF10a, was associated with constitutive suppression root branching independent of viral infection. In addition, overexpression of a microRNA-insensitive mutant of SlARF10a mimicked the effect of ToBRFV on root development, suggesting a specific role for SlARF10a in ToBRFV-mediated suppression of root branching. Taken together, our results provide new insights into the impact of tobamoviruses on root development and the role of ARF10a in the suppression of root branching in tomato.

The mutation of P53 is found in 50% of all human cancers, affecting the protein structure conformation, which further impacts its function. Identifying the appropriate protein structure for future research has been challenging. Many X-ray crystallography structures exist in the Protein Data Bank (PDB) for a given protein. We compared two proteins with different resolutions to determine whether the differences between the two structures were statistically significant. The present study used mutagenesis to study two structures of the protein P53 with various resolutions to assess how the conformation of the protein changes upon mutation. We used an AUTO-MUTE 2.0, which is a computational geometry method based on the Delaunay tessellation for predicting protein structures. The current study compares the prediction results obtained from different predictive methods. We used logistic regression models and corresponding receiver operating characteristic (ROC) curves to model the differences between structures using the variables available at PDB. We conclude from this study that x-ray crystallography is a sensitive and advanced technique, and the resulting proteins at different resolutions are similar.

Supplementary Material 1 List of participating ECT centres, included in the interprovincial analysis of the psychiatry dataset (N = 67)

Supplemental Material for Hospitalized patients with positive antiphospholipid antibodies who have low complement levels are at increased risk for death—a retrospective cohort study by Edward Itelman, Maxim Perelman, Natali Bivar, Daniella Kent, Adva Vaisman, Gad Segal, Liat Negru, Amir Dagan in Lupus

ResumenLa artrosis es una enfermedad progresiva de las articulaciones sinoviales que causa dolor, impotencia funcional, discapacidad, y degeneración progresiva de la articulación. En sus tratamientos, sobre todo en etapas tempranas, existen distintas intervenciones para evitar tanto su desarrollo y progresión como también para lograr un adecuado manejo de los síntomas, y hay tratamientos médicos orales no convencionales con evidencia controvertida. El objetivo de este trabajo es proporcionar una actualización, dirigida a especialistas en Ortopedia y Traumatología, respecto a la evidencia actual sobre las terapias complementarias orales en el tratamiento de la artrosis de rodilla. Se hace referencia a los métodos fármacológicos complementarios más usados y estudiados, mencionando el método de acción y las consecuencias estudiadas sobre la artrosis de rodilla. Se finaliza con una tabla de recomendaciones basada en evidencia actual.

What is the association between serum TSH and FT4 levels with functional decline in a group of older euthyroid patients at risk of frailty? For each 0.1 ng/dL increase in baseline and mean FT4 follow-up levels, the risks of functional decline increased by 14.1% and 7.7%, respectively. The risk of functional decline was almost 9 times higher in patients with a baseline level of FT4 in the fourth and fifth quintiles and 50% lower in those with a baseline level of FT4 in the first quintile. No association between TSH and the outcome was found. Higher and lower FT4 levels are, respectively, a risk and a protective factor for functional decline in these individuals. To assess the associations between TSH and free thyroxine (FT4) levels and decline in functional status in euthyroid older patients at risk of frailty. Longitudinal prospective study. Participants from the geriatric outpatient clinic of a university hospital, who fulfilled the criteria for frailty or were at risk of frailty, were recruited. Only those euthyroid, defined by age-specific reference range of TSH, were included. Serum was collected during enrollment and at the third and sixth years of follow-up to assess the mean value of all follow-up levels of serum TSH and FT4. Functional status assessing activities of daily living (ADL) and instrumental ADL were evaluated using the Katz Index and the Health Assessment Questionnaire, respectively. Functional decline was defined by a positive variation in any of the applied scales in the absence of disagreement between the scales or if the patient was institutionalized. Of the 273 participants (72.5% females) enrolled (mean age 80 years old), 48 died and 102 presented functional decline at the end of follow-up (mean 3.6 ± 1.7 years). Each 0.1 ng/dL increase in baseline and mean follow-up serum FT4 levels increased the risk of functional decline by 14.1% and 7.7%, respectively. The risk of functional decline was 9 times greater with baseline FT4 levels in the fourth and fifth quintiles (p = 0.049) and 50% lower with baseline FT4 levels in the first quintile (p = 0.046). No association between TSH and the outcome was found. Higher and lower FT4 levels were, respectively, a risk and a protective factor for the decline in functional status in a cohort of euthyroid older adults at risk of frailty.

Resumen: La historia de los inicios en Chile de la implementación nacional de las unidades de cuidados intensivos neonatales, y por ende de los inicios de la neonatología moderna en Chile, es de visionarios motivados exclusivamente por el profundo deseo de mejorar la sobrevida y calidad de vida de pequeños que nacían, muy a su pesar, antes de tiempo. Es una historia que, como muchas otras del desarrollo de la medicina, vale la pena relatar no solo por los logros que alcanzó, sino que también por el proceso de gestación y desarrollo en sí. Recordaremos para ello primero la historia de los orígenes y desarrollo del cuidado de los recién nacidos en el mundo, su avance gradual en el siglo XIX y principios del siglo XX, su consolidación a partir de la década de los 60, y finalmente su impulso en Chile con especial mención de la gestación del programa nacional de cuidados intensivos de prematuros en la década de los 80. Summary: The story of the onset of nationwide implementation of neonatal intensive care units in Chile, and therefore the beginnings of modern neonatology in Chile, is a story of visionaries motivated exclusively by a deep desire to improve the survival rate and quality of life of the little ones who were born, much to their regret, before their time. It is a story that, like many others of advances in medicine, is worth telling not only for the achievements acomplished but also for the gestation and development process itself. We’ll begin this story by recalling the history of the origins and development of newborn care in the world, its gradual growth in the 19th and early 20th centuries, its consolidation from the 1960s onward and finally its development in Chile, with special focus on the gestation of the national program of intensive care for premature infants in the 1980s.

Background Chronic pain is prevalent but difficult to treat in patients undergoing hemodialysis (HD). Effective and safe analgesics are limited in this patient population. Our aim of this feasibility study was to evaluate the safety of sublingual oil based medical cannabis for pain management in patients undergoing HD. Methods In a prospective randomized double-blind cross-over design, patients undergoing HD with chronic pain were assigned to one of 3 arms: BOL-DP-o-04-WPE Whole-plant extract (WPE), BOL-DP-o-04 cannabinoid extraction (API) or placebo. WPE and API contained trans-delta9-‏tetrahydrocannabinol (THC) and Cannabidiol (CBD) in 1:6 ratio (1:6, THC: CBD). Patients were treated for 8 weeks, with subsequent 2-weeks wash out, followed by a cross-over to a different arm. The primary endpoint was safety. Results Eighteen patients were recruited and 15 were randomized. Three did not complete drug titration period due to adverse events (AEs) and one patient died during titration due to sepsis (WPE). Of those who completed at least one treatment period, 7 patients were in WPE arm, 5 in API and 9 in placebo. Most common AEs were sleepiness, which improved after dose reduction or patient adaptation. Most AEs were mild to moderate and resolved spontaneously. Serious AEs considered related to study drug included one episode of accidental overdose (WPE) leading to hallucinations. Liver enzymes were stable during cannabis treatment. Conclusions Short term medical cannabis use in patients treated with HD was generally well tolerated. The safety data supports further studies to assess the overall risk-benefit of a treatment paradigm utilizing medical cannabis to control pain in this patient population.