Conversion of a classical microbiology laboratory to a total automation laboratory enhanced by the application of lean principles.

Laboratory automation in microbiology improves productivity and reduces sample turnaround times (TATs). However, its full potential can be unlocked through the optimization of workflows by adopting lean principles. This study aimed to explore the relative impact of laboratory automation and continuous improvement events (CIEs) on productivity and TATs. Laboratory automation took place in November 2020 and consisted of the introduction of WASPLab and VITEK MS systems. CIEs were run in May and September 2021. Before the conversion, the laboratory processed about ~492 samples on weekdays and had 10 full-time equivalent (FTE) staff for a productivity of 49 samples/FTE/day. In March 2021, after laboratory automation, the caseload went up to ~621 while the FTEs decreased to 8.5, accounting for productivity improvement to 73 samples/FTE/day. The hypothetical productivity went up to 110 samples/FTE/day following CIEs, meaning that the laboratory could at that point deal with a caseload increase to ~935 with unchanged FTEs. Laboratory conversion also led to an improvement in TATs for all sample types. For vaginal swabs and urine samples, median TATs decreased from 70.3 h [interquartile range (IQR): 63.5-93.1] and 73.7 h (IQR: 35.6-50.7) to 48.2 h (IQR: 44.8-67.7) and 40.0 h (IQR: 35.6-50.7), respectively. Automation alone was responsible for 37.2% and 75.8% of TAT reduction, respectively, while the remaining reduction of 62.8% and 24.2%, respectively, was achieved due to CIEs. The laboratory reached productivity and TAT goals predefined by the management after CIEs. In conclusion, automation substantially improved productivity and TATs, while the subsequent implementation of lean management further unlocked the potential of laboratory automation.IMPORTANCEIn this study, we combined total laboratory automation with lean management to show that appropriate laboratory work organization enhanced the benefit of the automation and substantially contributed to productivity improvements. Globally, the rapid availability of accurate results in the setting of a clinical microbiology laboratory is part of patient-centered approaches to treat infections and helps the implementation of antibiotic stewardship programs backed by the World Health Organization. Locally, from the point of view of laboratory management, it is important to find ways of maximizing the benefits of the use of technology, as total laboratory automation is an expensive investment.

What is the duration of untreated psychosis worldwide? - A meta-analysis of pooled mean and median time and regional trends and other correlates across 369 studies.

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, reporting mean ± s.d. or median DUP in patients with first episode psychosis (FEP), without language restrictions. We conducted random-effect meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO:CRD42020163640). From 12 461 citations, 369 studies were included. The mean DUP was 42.6 weeks (95% confidence interval (CI) 40.6-44.6, k = 283, n = 41 320), varying significantly across continents (p < 0.001). DUP was (in descending order) 70.0 weeks (95% CI 51.6-88.4, k = 11, n = 1508) in Africa; 48.8 weeks (95% CI 43.8-53.9, k = 73, n = 12 223) in Asia; 48.7 weeks (95% CI 43.0-54.4, k = 36, n = 5838) in North America; 38.6 weeks (95% CI 36.0-41.3, k = 145, n = 19 389) in Europe; 34.9 weeks (95% CI 23.0-46.9, k = 11, n = 1159) in South America and 28.0 weeks (95% CI 20.9-35.0, k = 6, n = 1203) in Australasia. There were differences depending on the income of countries: DUP was 48.4 weeks (95% CI 43.0-48.4, k = 58, n = 5635) in middle-low income countries and 41.2 weeks (95% CI 39.0-43.4, k = 222, n = 35 685) in high income countries. Longer DUP was significantly associated with older age (ß = 0.836, p < 0.001), older publication year (ß = 0.404, p = 0.038) and higher proportion of non-White FEP patients (ß = 0.232, p < 0.001). Median DUP was 14 weeks (Interquartile range = 8.8-28.0, k = 206, n = 37 215). In conclusion, DUP is high throughout the world, with marked variation. Efforts to identify and intervene sooner in patients with FEP, and to promote global mental health and access to early intervention services (EIS) are critical, especially in developing countries.

Autism spectrum disorder and obstetric optimality: a twin study and meta-analysis of sibling studies.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a strong genetic basis. Recent studies have suggested that its aetiology is also influenced by environmental factors. Some of the most examined environmental factors are obstetric complications. However, the results are inconsistent. METHODS: We aimed to explore the association between obstetric complications and autism in a population-based twin sample using the Obstetric Enquiry Scale (OES), a scale that measures the presence or absence of pre-, peri- and neonatal factors. Additionally, we report the meta-analytic results for obstetrical factors reported in previously published sibling studies. RESULTS: Our study included 115 cases pairs and 62 controls pairs and showed that children with autism and their unaffected co-twins present significantly more obstetric complications than controls (ASD vs. controls ß 1.26, CI 95% 1.11-1.40 p < .001; unaffected co-twin vs. controls ß 1.20, 95% CI 1.07-1.36 p < .003). However, we did not find statistically significant differences between children with ASD and their unaffected co-twins (ß .96, 95% CI 0.85-1.09, p 0.55). Meta-analysis demonstrated that maternal hypertension (RR 1.35, CI 95% 1.23-1.48), uterine bleeding (RR 1.20 CI 95% 1.01-1.42) and exposure to antibiotic during pregnancy (1.11 CI 95% 1.00-1.22) increase risk of ASD. CONCLUSIONS: This study confirms that children with ASD and their unaffected twins show more obstetric complications than controls. However, these complications do not distinguish between ASD twins and their unaffected co-twins. In addition, the meta-analysis showed little influence of birth factors on ASD which suggests a shared familial liability for both obstetric complications and autism, rather than a causal association.

Significados del cuidado construidos por cuidadores de personas mayores / Significance of caring built by caretakers of elderly people / Significado do cuidado construido por cuidadores de pessoas idosas

ntroducción: En el marco de un proceso formativo en 5 ciudades de Colombia, impartido por la Universidad de Antioquia y financiado por PROTECCIÓN S.A. entre los años 2018 ­ 2020, se planteó como obje-tivo: analizar los significados del cuidado que construyen los cuidadores de personas mayores en las ciudades de Rionegro, Bogotá, Cali, Pereira y Medellín. Materiales y métodos: 202 participantes, con edades com-prendidas entre los 21 y los 73 años. Se desarrolló un estudio etnográfico particularista y colaborativo. Se realizaron 6 entrevistas individuales a cuidadores y expertos; se desarrolló observación participante y no parti-cipante de las clases del diplomado y de algunos contextos de cuidado. Resultados: El amor, la preservación de la existencia, el servicio, el sentido de vida y la responsabilidad fueron los significados que sobresa-lieron en los cuidadores de personas mayores, la transformación de es-tos significados se denota en la dedicación que destinan para la persona mayor cuidada, permitiendo incluso, una perspectiva de autocuidado. Conclusiones: La labor de cuidar es un acto que compromete la vida emocional tanto del cuidador como de la persona mayor cuidada. Se identificó que el proceso de formación favoreció la creación de redes de cuidadores, los cuáles en la medida del proceso formativo, evidenciaron capacidad de transformar visiones y significados; replantear situaciones particulares; comprender la necesidad de cuidar de sí, para cuidar a otro; la creación de lazos de solidaridad; las experiencias del trabajo interdis-ciplinar y el interés por capacitarse y compartir conocimientos.

Introduction: Within the framework of a training process in 5 cities of Colombia, given by the University of Antioquia and financed by PROTECCIÓN S.A. between the years 2018 - 2020, the objective was set: to analyze the meanings of the care that the caregivers of the elderly build in the cities of Rionegro, Bogotá, Cali, Pereira and Medellín. Materials and methods: 202 participants, between 21 and 73 years old. A particularist and collaborative ethnographic study was developed. Six individual interviews were conducted with caregivers and experts; participant and non-parti-cipant observation of the diploma classes and some care contexts was developed. Results: love, preservation of existence, service, meaning of life and responsibility were the meanings that stood out in the caregivers of older people, the transformation of these meanings is denoted in the de-dication they give to the older person being cared for, even allowing a perspective of self-care. Conclusions: the work of caring is an act that compromises the emotional life of both the care-giver and the elderly carer. It was identified that the formation process favored the creation of caregivers' networks, which in the measure of the formation process, showed capacity to trans-form visions and meanings; to rethink particular situations; to understand the need to take care of oneself, to take care of another; the creation of solidarity ties; the experiences of interdisciplinary work and the interest in training and sharing knowledge

Introdução: No marco do processo formativo em cinco cidades da Colômbia, oferecido pela Universidade de Antioquia e financiado por PROTECCIÓN S.A entre os anos 2018 e 2020 plan-teou-se o objetivo de analisar os significados de cuidado construídos por cuidadores de pessoas idosas nas cidades de Rionegro, Bogotá, Cali, Pereira e Medellín. Materiais e métodos: 202 participantes, com idades entre 21 e 73 anos. Desenvolveu-se um estudo etnográfico particularista e colaborativo, realizaram-se 6 entrevistas individuais a cuidadores e expertos; desenvolveu-se observação participante e não participante das aulas do curso e de alguns contextos de cuidado. Resultados: O amor, a preservação da existência, o serviço, o sentido da vida e a responsabili-dade foram os significados que se destacaram nos cuidadores de pessoas idosas. A transformação desses significados evidenciou-se na dedicação à pessoa idosa, permitindo incluso a perspectiva do autocuidado. Conclusões: O papel de cuidar é um ato que compromete a vida emocional tanto do cuidador como da pessoa idosa cuidada, identificou-se que o processo de formação favorecei a criação de redes de cuidadores, os quais na medida do processo formativo, evidenciaram capaci-dade de transformar visões e significados; reformular situações particulares; compreender a neces-sidade de cuidar de si para cuidar ao outro; a criação de alianças de solidariedade; as experiências do trabalho interdisciplinar e o interesse por capacitar-se e compartir conhecimentos.

Personas en proceso de reintegración mayores (PPRM) en Colombia, retos para su reintegración / Senior Citizens in the Reintegration Process (PPRM) in Colombia: Challenges for their reintegration

Resumen Al analizar la Ruta de reintegración de la Agencia para la Reincorporación y la Normalización (ARN) para las Personas mayores en Colombia que han hecho parte de grupos armados al margen de la ley e inician procesos de reintegración a la vida civil, en el Estado Colombiano, se deja entrever por una lado que, esta población es especialmente vulnerable en tanto tienen más dificultad para adaptarse a la vida civil, advierte de la necesidad de reconocer los vacíos que exigen emplear enfoques diferenciales para abordar de forma adecuada las condiciones y necesidades particulares de este conjunto poblacional, destaca además, la importancia de aumentar o mejorar la oferta pública y privada de servicios que permitan una atención integral y sostenible.

Abstract By analyzing the Route of Reintegration of the Agency for Reintegration and Standardization (ARN) for senior citizens in Colombia, who have been part of illegal armed groups and initiate processes of reintegration into the civilian life, in the Colombian State, it is evident, on the one hand, that this population is especially vulnerable as they have more difficulty adapting to the civilian life. It warns of the need to recognize the gaps that require particular conditions and needs of this population group. It further stresses the importance of increasing and/or improving the public and private offer of services, which allow comprehensive and sustainable care.

Applications of Developmental Psychopathology.

Developmental psychopathology studies the basic mechanisms, including not only biological factors but also environmental and social factors that may interact with them, by means of which developmental pathways deviate toward pathological or typical outcomes. Family studies conducted during the last century show substantial evidence of heritability among psychiatric disorders. Besides, a large number of genes implicated in shaping the development of the central nervous system have been related to psychiatric conditions. In addition, there is a wide range of stressors and harmful agents that, when acting on sensitive developmental periods, might damage brain function and generate or precipitate psychopathology over time. All these factors have the potential to change the way disorders with a neurodevelopmental origin are expressed, including their age of appearance and clinical manifestations. Both symptoms and social impairment need to be considered in clinical evaluations, as treatment is unlikely to be effective if the problem has not been characterized correctly or if the patients' particular characteristics, which change throughout development, are not taken into consideration.

Eosinofilia y serositis inducida por clozapina / Clozapine-induced eosinophilia and serositis

No disponible

Developmental Differences Between Schizophrenia and Bipolar Disorder.

Ample evidence supports a neurodevelopmental origin in some cases of schizophrenia (SZ). More inconsistent information is available for bipolar disorder (BD). We herein review studies with a focus on premorbid (adjustment and functionality) and early developmental milestones that include both SZ and BD patients. A search was performed in the PubMed electronic database, retrieving 619 abstracts; 30 were ultimately included in this systematic review. Eight prospective cohorts, 15 retrospective studies, and 7 studies based on national registries. Psychomotor developmental deviations and general adjustment problems characterize the childhood of subjects later diagnosed with SZ or BD; they are more marked in those later diagnosed with SZ vs BD, earlier onset vs later onset, and psychotic vs nonpsychotic disorders. Cognitive impairment follows a linear risk trend for SZ and a U-shaped trend for BD. Social isolation and visuoperceptual/reading anomalies more frequently antecede SZ. Pervasive developmental disorders increase the risk for both SZ and BD, more so in cases with normal intelligence. The predictive risk of each isolated developmental marker is low, but a significant percentage of subjects with SZ and a minority of adults with BD showed signs of premorbid abnormalities in childhood. The great limitation is still the lack of studies comparing SZ and BD that include psychotic and nonpsychotic bipolar cases separately. There are many cases, even in childhood/adolescent SZ, where no premorbid anomalies are found, and immunological disorders or other etiologies should be searched for. At least in cases with clear neurodevelopmental markers, rare genetic variants should be investigated.

HIV protease inhibitors induce senescence and alter osteoblastic potential of human bone marrow mesenchymal stem cells: beneficial effect of pravastatin.

HIV-infected patients receiving antiretroviral therapy present an increased prevalence of age-related comorbidities, including osteoporosis. HIV protease inhibitors (PIs) have been suspected to participate to bone loss, but the mechanisms involved are unknown. In endothelial cells, some PIs have been shown to induce the accumulation of farnesylated prelamin-A, a biomarker of cell aging leading to cell senescence. Herein, we hypothesized that these PIs could induce premature aging of osteoblast precursors, human bone marrow mesenchymal stem cells (MSCs), and affect their capacity to differentiate into osteoblasts. Senescence was studied in proliferating human MSCs after a 30-day exposure to atazanavir and lopinavir with or without ritonavir. When compared to untreated cells, PI-treated MSCs had a reduced proliferative capacity that worsened with increasing passages. PI treatment led to increased oxidative stress and expression of senescence markers, including prelamin-A. Pravastatin, which blocks prelamin-A farnesylation, prevented PI-induced senescence and oxidative stress, while treatment with antioxidants partly reversed these effects. Moreover, senescent MSCs presented a decreased osteoblastic potential, which was restored by pravastatin treatment. Because age-related bone loss is associated with increased bone marrow fat, we also evaluated the capacity of PI-treated MSCs to differentiate into adipocyte. We observed an altered adipocyte differentiation in PI-treated MSCs that was reverted by pravastatin. We have shown that some PIs alter osteoblast formation by affecting their differentiation potential in association with altered senescence in MSCs, with a beneficial effect of statin. These data corroborate the clinical observations and allow new insight into pathophysiological mechanisms of PI-induced bone loss in HIV-infected patients.

Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet.

Western diet is characterized by a hypercaloric and hyperlipidic intake, enriched in saturated fats, that is associated with the increased occurrence of metabolic diseases. To cope with this overload of dietary lipids, the intestine, which delivers dietary lipids to the body, has to adapt its capacity in lipid absorption and lipoprotein synthesis. We have studied the early effects of a high-fat diet (HFD) on intestinal lipid metabolism in mice. After 7 days of HFD, mice displayed normal fasting triglyceridemia but postprandial hypertriglyceridemia. HFD induced a decreased number of secreted chylomicrons with increased associated triglycerides. Secretion of larger chylomicrons was correlated with increased intestinal microsomal triglyceride transfer protein (MTP) content and activity. Seven days of HFD induced a repression of genes involved in fatty acid synthesis (FAS, ACC) and an increased expression of genes involved in lipoprotein assembly (apoB, MTP, and apoA-IV), suggesting a coordinated control of intestinal lipid metabolism to manage a high-fat loading. Of note, the mature form of the transcription factor SREBP-1c was increased and translocated to the nucleus, suggesting that it could be involved in the coordinated control of gene transcription. Activation of SREBP-1c was partly independent of LXR. Moreover, HFD induced hepatic insulin resistance whereas intestine remained insulin sensitive. Altogether, these results demonstrate that a short-term HFD is sufficient to impact intestinal lipid metabolism, which might participate in the development of dyslipidemia and metabolic diseases.

Inhibition of monoamine oxidases desensitizes 5-HT1A autoreceptors and allows nicotine to induce a neurochemical and behavioral sensitization.

Although nicotine is generally considered to be the main compound responsible for addictive properties of tobacco, experimental data indicate that nicotine does not exhibit all the characteristics of other substances of abuse. We recently showed that a pretreatment with mixed irreversible monoamine oxidases inhibitors (MAOIs), such as tranylcypromine, triggers a locomotor response to nicotine in mice and allows maintenance of behavioral sensitization to nicotine in rats. Moreover, we showed by microdialysis in mice that behavioral sensitization induced by compounds belonging to main groups of drugs of abuse, such as amphetamine, cocaine, morphine, or alcohol, was underlain by sensitization of noradrenergic and serotonergic neurons. Here, this neurochemical sensitization was tested after nicotine, tranylcypromine, or a mixture of both compounds. Data indicate that, whereas neither repeated nicotine nor repeated tranylcypromine alone has any effect by itself, a repeated treatment with a mixture of nicotine and tranylcypromine induces both behavioral sensitization and sensitization of noradrenergic and serotonergic neurons. The development of neurochemical and behavioral sensitizations is blocked by prazosin and SR46349B [(1Z,2E)-1-(2-fluoro-phenyl)-3-(4-hydroxyphenyl)-prop-2-en-one-O-(2-dimethylamino-ethyl)-oxime hemifumarate], two antagonists of alpha1b-adrenergic and 5-HT(2A) receptors, respectively, but not by SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride], a D(1) receptor antagonist. Finally, we found that pretreatments with WAY 100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-hexane carboxamide trihydrochloride], a 5-HT(1A) receptor antagonist, can also induce a behavioral and neurochemical sensitization to repeated nicotine. Complementary experiments with 8-OHDPAT (8-hydroxy-dipropylamino-tetralin), a 5-HT(1A) receptor agonist, and analysis of 5-HT(1A) receptors expression in the dorsal raphe nucleus after a tranylcypromine injection indicate that MAOIs contained in tobacco desensitize 5-HT(1A) autoreceptors to trigger the strong addictive properties of tobacco.

Aspectos generales de la automatización industrial del sector farmacéutico / General aspects about the industrial automation in pharmaceuticals

El presente artículo recopila la información sobre las tendencias mundiales en automatización de procesos industriales, aplicados al campo de los procesos de transformación de materiales en el sector farmacéutico. Se plantean los diferentes niveles de automatización que pueden ser de interés para la industria farmacéutica nacional y se hace una reflexión sobre el grado de avance para nuestra industria, seleccionando información sobre casos exitosos de automatización llevados a cabo desde la academia para el sector

Apple procyanidins decrease cholesterol esterification and lipoprotein secretion in Caco-2/TC7 enterocytes.

Decrease of plasma lipid levels by polyphenols was linked to impairment of hepatic lipoprotein secretion. However, the intestine is the first epithelium that faces dietary compounds, and it contributes to lipid homeostasis by secreting triglyceride-rich lipoproteins during the postprandial state. The purpose of this study was to examine the effect of apple and wine polyphenol extracts on lipoprotein synthesis and secretion in human Caco-2/TC7 enterocytes apically supplied with complex lipid micelles. Our results clearly demonstrate that apple, but not wine, polyphenol extract dose-dependently decreases the esterification of cholesterol and the enterocyte secretion of lipoproteins. Apple polyphenols decrease apolipoprotein B (apoB) secretion by inhibiting apoB synthesis without increasing the degradation of the newly synthesized protein. Under our conditions, cholesterol uptake, apoB mRNA, and microsomal triglyceride protein activity were not modified by apple polyphenols. The main monomers present in our mixture did not interfere with the intestinal lipid metabolism. By contrast, apple procyanidins reproduced the inhibition of both cholesteryl ester synthesis and lipoprotein secretion. Overall, our results are compatible with a mechanism of action of polyphenols resulting in impaired lipid availability that could induce the inhibition of intestinal lipoprotein secretion and contribute to the hypolipidemic effect of these compounds in vivo.