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The pathogenesis of COVID-19 warrants unravelling. Genetic polymorphism analysis may help answer the variability in disease outcome. To determine the role of KIR and HLA polymorphisms in susceptibility, progression, and severity of SARS-CoV-2 infection, 458 patients and 667 controls enrolled in this retrospective observational study from April to December 2020. Mild/moderate and severe/death study groups were established. HLA-A, -B, -C, and KIR genotyping were performed using the Lifecodes® HLA-SSO and KIR-SSO kits on the Luminex® 200™ xMAP fluoroanalyser. A probability score using multivariate binary logistic regression analysis was calculated to estimate the likelihood of severe COVID-19. ROC analysis was used to calculate the best cut-off point for predicting a worse clinical outcome with high sensitivity and specificity. A p ≤ 0.05 was considered statistically significant. KIR AA genotype protected positively against severity/death from COVID-19. Furthermore, KIR3DL1, KIR2DL3 and KIR2DS4 genes protected patients from severe forms of COVID-19. KIR Bx genotype, as well as KIR2DL2, KIR2DS2, KIR2DS3 and KIR3DS1 were identified as biomarkers of severe COVID-19. Our logistic regression model, which included clinical and KIR/HLA variables, categorised our cohort of patients as high/low risk for severe COVID-19 disease with high sensitivity and specificity (Se = 94.29%, 95% CI [80.84-99.30]; Sp = 84.55%, 95% CI [79.26-88.94]; OR = 47.58, 95%CI [11.73-193.12], p < 0.0001). These results illustrate an association between KIR/HLA ligand polymorphism and different COVID-19 outcomes and remarks the possibility of use them as a surrogate biomarkers to detect severe patients in possible future infectious outbreaks.
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COVID-19 , Receptores KIR , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Receptores KIR/genética , Masculino , Feminino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Projetos Piloto , Estudos Retrospectivos , Polimorfismo Genético , Idoso , Genótipo , Predisposição Genética para Doença , Adulto , Índice de Gravidade de Doença , Antígenos HLA/genéticaRESUMO
The XVI Post-ECTRIMS meeting was held in Seville on 20 and 21 October 2023, where expert neurologists in multiple sclerosis (MS) summarised the main new developments presented at the ECTRIMS 2023 congress, which took place in Milan from 11 to 13 October. The aim of this article is to summarise the content presented at the Post-ECTRIMS Meeting, in an article in two parts. This second part covers the health of women and elderly MS patients, new trends in the treatment of cognitive impairment, focusing particularly on meditation, neuroeducation and cognitive rehabilitation, and introduces the concept of fatigability, which has been used to a limited extent in MS. The key role of digitalization and artificial intelligence in the theoretically near future is subject to debate, along with the potential these technologies can offer. The most recent research on the various treatment algorithms and their efficacy and safety in the management of the disease is reviewed. Finally, the most relevant data for cladribine and evobrutinib are presented, as well as future therapeutic strategies currently being investigated.
TITLE: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (II).Los días 20 y 21 de octubre se celebró en Sevilla la XVI edición de la reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso del ECTRIMS 2023, celebrado en Milán del 11 al 13 de octubre. El objetivo de este artículo es sintetizar las ponencias que tuvieron lugar en la reunión Post-ECTRIMS en un artículo desglosado en dos partes. En esta segunda parte se abordan la salud de la mujer y del paciente mayor con EM, las nuevas tendencias en el tratamiento del deterioro cognitivo, con especial mención a la meditación, la neuroeducación y la rehabilitación cognitiva, y se introduce el concepto de fatigabilidad, poco utilizado en la EM. El papel clave de la digitalización y la inteligencia artificial en un futuro teóricamente cercano es objeto de debate, junto con las expectativas que pueden ofrecer. Se repasa la investigación más reciente sobre los distintos algoritmos de tratamiento, y su eficacia y seguridad en el manejo de la enfermedad. Por último, se exponen los datos más relevantes sobre la cladribina y el evobrutinib, y se presentan las futuras estrategias terapéuticas actualmente en investigación.
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Congressos como Assunto , Esclerose Múltipla , Idoso , Feminino , Humanos , Masculino , Esclerose Múltipla/terapiaRESUMO
The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS. The contributions of innate immunity and central nervous system resident cells, including macrophages and microglia in MS pathophysiology and as therapeutic targets were discussed. Compartmentalised intrathecal inflammation was recognised as central to understanding the progression of MS, and the relationship between inflammatory infiltrates and disease progression was highlighted. Perspectives in demyelinating pathologies were reviewed, focusing on neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease, highlighting their pathophysiological and diagnostic differences compared to MS. Advances in neuroimaging were also discussed, and especially the analysis of active chronic lesions, such as paramagnetic rim lesions. In the absence of clinical improvements in trials of remyelinating treatments, methodological strategies to optimise the design of future studies were proposed. Breakthroughs in detecting the prodromal phase of MS, the use of biomarkers in body fluids to assess activity, progression and treatment response, and research on progression independent of flares were addressed. The need to define criteria for radiologically isolated syndrome and to clarify the concept was also discussed.
TITLE: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).La XVI edición de la reunión Post-ECTRIMS se celebró los días 20 y 21 de octubre de 2023 en Sevilla. Este encuentro reunió a neurólogos especialistas en esclerosis múltiple (EM) de España, quienes compartieron un resumen de las innovaciones más destacables del congreso ECTRIMS, acontecido en Milán la semana anterior. El objetivo de este artículo es sintetizar las novedades relativas a la patogenia, el diagnóstico y el pronóstico de la EM. Se destacaron las contribuciones de la inmunidad innata y las células residentes del sistema nervioso central, incluyendo macrófagos y microglía, en la patofisiología de la EM y como objetivos terapéuticos. La inflamación intratecal compartimentada se reconoció como fundamental para entender la progresión de la EM, y destaca la relación entre infiltrados inflamatorios y la evolución de la enfermedad. Se revisaron perspectivas en patologías desmielinizantes, enfocadas en la neuromielitis óptica y la enfermedad asociada a anticuerpos contra la glucoproteína de mielina de oligodendrocitos, subrayando sus distinciones patofisiológicas y diagnósticas con la EM. También se abordaron los avances en neuroimagen, especialmente en el análisis de las lesiones crónicas activas, como las lesiones con borde paramagnético. Ante la ausencia de mejoras clínicas en ensayos de tratamientos remielinizantes, se propusieron estrategias metodológicas para optimizar el diseño de futuros estudios. Se abordaron los avances en la detección de la fase prodrómica de la EM, el uso de biomarcadores en fluidos corporales para evaluar la actividad, la progresión y la respuesta al tratamiento, y la investigación sobre la progresión independiente de la actividad de brote. Además, se debatió sobre la necesidad de definir criterios para el síndrome radiológico aislado o precisar su concepto.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/terapia , Congressos como AssuntoRESUMO
Disrupted or atypical light-dark cycles disrupts synchronization of endogenous circadian clocks to the external environment; extensive circadian rhythm desynchrony promotes adverse health outcomes. Previous studies suggest that disrupted circadian rhythms promote neuroinflammation and neuronal damage post-ischemia in otherwise healthy mice, however, few studies to date have evaluated these health risks with aging. Because most strokes occur in aged individuals, we sought to identify whether, in addition to being a risk factor for poor ischemic outcome, circadian rhythm disruption can increase risk for vascular cognitive impairment and dementia (VCID). We hypothesized that repeated 6 h phase advances (chronic jet lag; CJL) for 8 weeks alters cerebrovascular architecture leading to increased cognitive impairments in aged mice. Female CJL mice displayed impaired spatial processing during a spontaneous alternation task and reduced acquisition during auditory-cued associative learning. Male CJL mice displayed impaired retention of the auditory-cued associative learning task 24 h following acquisition. CJL increased vascular tortuosity in the isocortex, associated with increased risk for vascular disease. These results demonstrate that CJL increased sex-specific cognitive impairments coinciding with structural changes to vasculature in the brain. We highlight that CJL may accelerate aged-related functional decline and could be a crucial target against disease progression.
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Ritmo Circadiano , Demência Vascular , Animais , Camundongos , Masculino , Feminino , Ritmo Circadiano/fisiologia , Fotoperíodo , Reconhecimento Psicológico , Demência Vascular/etiologia , CogniçãoRESUMO
Ligation of the intersphincteric fistula tract has been recently employed as definitive treatment of anal fistulas. However, it carries a potential risk of continence impairment, fistula recurrence, and repeated operations. This study aimed to assess postoperative outcomes related to this procedure and evaluate the potential influence of preoperative and intraoperative features. Patients who underwent LIFT procedure between June 2012 and September 2021 were retrospectively analyzed. Patients were divided according to whether they developed fistula recurrence and on the history of a surgery prior to the LIFT. Preoperative features, postoperative outcomes, and risk factors adverse outcomes were analyzed. Forty-eight patients were included, of which 25 received primary LIFT, being the high transsphincteric fistula pattern the most frequent (62.5%). The median follow-up was 13.3 months, with a recurrence rate of 20.8%, of which the majority presented an intersphincteric fistula pattern (50%); and continence impairment rate of 16.7%. A higher prevalence of diabetes (p = 0.026) and a trend towards a higher prevalence of patients with a history of high transsphincteric fistula (0.052) were observed in the group with fistula recurrence. The history of diabetes and the operation time with a cut-off value ≥ 69 min showed a trend as a risk factors for developing fistula recurrence (0.06) and postoperative continence impairment (0.07), respectively. The LIFT procedure seems to be safe in terms of morbidity, with a reasonable incidence of recurrences, showing better results when it is primarily performed. Preoperative characteristics should be considered as they may impact outcomes.
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Incontinência Fecal , Complicações Pós-Operatórias , Fístula Retal , Recidiva , Humanos , Fatores de Risco , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fístula Retal/cirurgia , Resultado do Tratamento , Incontinência Fecal/etiologia , Incontinência Fecal/epidemiologia , Adulto , Ligadura/métodos , Idoso , Seguimentos , Canal Anal/cirurgia , Duração da Cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversosRESUMO
Circadian rhythms are endogenous biological cycles that regulate physiology and behavior and are set to precisely 24-h by light exposure. Light at night (LAN) dysregulates physiology and function including immune response; a critical component that contributes to stroke pathophysiological progression of neuronal injury and may impair recovery from injury. The goal of this study is to explore the effects of dim LAN (dLAN) in a murine model of ischemic stroke to assess how nighttime lighting from hospital settings can affect stroke outcome. Further, this study sought to identify mechanisms underlying pathophysiological changes to immune response after circadian disruption. Male and female adult Swiss Webster (CFW) mice were subjected to transient or permanent focal cerebral ischemia, then were subsequently placed into either dark night conditions (LD) or one night of dLAN (5 lx). 24 h post-stroke, sensorimotor impairments and infarct sizes were quantified. A single night of dLAN following MCAO increased infarct size and sensorimotor deficits across both sexes and reduced survival in males after 24 h. Flow cytometry was performed to assess microglial phenotypes after MCAO, and revealed that dLAN altered the percentage of microglia that express pro-inflammatory markers (MHC II+ and IL-6) and microglia that express CD206 and IL-10 that likely contributed to poor ischemic outcomes. Following these results, microglia were reduced in the brain using Plexxikon 5622 (PLX 5622) a CSFR1 inhibitor, then the mice received an MCAO and were exposed to LD or dLAN conditions for 24 h. Microglial depletion by PLX5622 resulted in infarct sizes that were comparable between lighting conditions. This study provides supporting evidence that environmental lighting exacerbates ischemic injury and post-stroke mortality by a biological mechanism that exposure to dLAN causes a fundamental shift of activated microglial phenotypes from beneficial to detrimental at an early time point after stroke, resulting in irreversible neuronal death.
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AVC Isquêmico , Microglia , Animais , Microglia/patologia , Microglia/metabolismo , Camundongos , Masculino , Feminino , AVC Isquêmico/patologia , Luz/efeitos adversos , Ritmo Circadiano/fisiologia , Isquemia Encefálica/patologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/patologiaRESUMO
Aging is a risk factor for the development of breast cancer. Foundational science studies have supported associations among neuroinflammation, breast cancer, and chemotherapy, but to date, these associations are based on studies using young adult rodents. The current study examined the neuroinflammatory effects of chemotherapy in aged, tumor-naïve and tumor-bearing mice with or without social enrichment. Mice received two intravenous injections of doxorubicin (A) and cyclophosphamide (C) at a two-week interval. Brain immune cells were enriched/assessed via flow cytometry, seven days following the second chemotherapy injection. Social enrichment enhanced peripheral immune cell trafficking in aged tumor-naive mice treated with AC. Group housed aged tumor bearing mice receiving AC had reduced percentage of IL-6+ monocytes and granulocytes relative to their singly housed counterparts. Notably, group housing aged experimental mice with young cage partners significantly reduced TNF + monocytes, tumor volume, and tumor mass. These data illustrate the importance of social enrichment in attenuating neuroinflammation and are the first to demonstrate that social support with young housing partners reduces tumor growth in aged mice.
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Fecal incontinence is the involuntary passage or the incapacity to control the release of fecal matter through the anus. It is a condition that significantly impairs quality of life in those that suffer from it, given that it affects body image, self-esteem, and interferes with everyday activities, in turn, favoring social isolation. There are no guidelines or consensus in Mexico on the topic, and so the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, neurogastroenterologists, and surgeons) to carry out the «Mexican consensus on fecal incontinence¼ and establish useful recommendations for the medical community. The present document presents the formulated recommendations in 35 statements. Fecal incontinence is known to be a frequent entity whose incidence increases as individuals age, but one that is under-recognized. The pathophysiology of incontinence is complex and multifactorial, and in most cases, there is more than one associated risk factor. Even though there is no diagnostic gold standard, the combination of tests that evaluate structure (endoanal ultrasound) and function (anorectal manometry) should be recommended in all cases. Treatment should also be multidisciplinary and general measures and drugs (lidamidine, loperamide) are recommended, as well as non-pharmacologic interventions, such as biofeedback therapy, in selected cases. Likewise, surgical treatment should be offered to selected patients and performed by experts.
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Incontinência Fecal , Humanos , Incontinência Fecal/diagnóstico , Incontinência Fecal/terapia , Incontinência Fecal/etiologia , Consenso , México/epidemiologia , Qualidade de Vida , Loperamida/uso terapêuticoRESUMO
The structure and function of the cardiovascular system are modulated across the day by circadian rhythms, making this system susceptible to circadian rhythm disruption. Recent evidence demonstrated that short-term exposure to a pervasive circadian rhythm disruptor, artificial light at night (ALAN), increased inflammation and altered angiogenic transcripts in the hippocampi of mice. Here, we examined the effects of four nights of ALAN exposure on mouse hippocampal vascular networks. To do this, we analyzed 2D and 3D images of hippocampal vasculature and hippocampal transcriptomic profiles of mice exposed to ALAN. ALAN reduced vascular density in the CA1 and CA2/3 of female mice and the dentate gyrus of male mice. Network structure and connectivity were also impaired in the CA2/3 of female mice. These results demonstrate the rapid and potent effects of ALAN on cerebrovascular networks, highlighting the importance of ALAN mitigation in the context of health and cerebrovascular disease.
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INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.
TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.
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Disfunção Cognitiva , Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Gravidez , Feminino , Humanos , Idoso , Esclerose Múltipla/tratamento farmacológico , PrevisõesRESUMO
INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented. It describes emerging biomarkers in body fluids and imaging findings that are predictive of disease progression and useful in the differential diagnosis of MS. It also discusses advances in imaging techniques which, together with a better understanding of the agents involved in demyelination and remyelination processes, provide a basis for dealing with remyelination in the clinical setting. Finally, the mechanisms triggering the inflammatory reaction and neurodegeneration involved in MS pathology are reviewed.
TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la XV edición de la Reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado en Ámsterdam entre el 26 y el 28 de octubre. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta primera parte se presentan los primeros eventos involucrados en el inicio de la EM, la implicación de los linfocitos y la migración de células del sistema inmunitario hacia el sistema nervioso central. Se describen los biomarcadores emergentes en fluidos corporales y los hallazgos de imagen que permiten predecir la evolución de la enfermedad, y que resultan útiles en el diagnóstico diferencial de la EM. También se exponen los avances en las técnicas de imagen que, junto con un mayor conocimiento de los agentes involucrados en los procesos de desmielinización y remielinización, proporcionan una base para abordar la remielinización en el entorno clínico. Por último, se repasan los mecanismos desencadenantes de la reacción inflamatoria y la neurodegeneración implicados en la patología de la EM.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Sistema Nervoso Central , Biomarcadores , Inflamação , Progressão da DoençaRESUMO
BACKGROUND: The choice of bronchodilators for responsiveness testing (BRT) is a clinical decision according to ATS/ERS. Since January 2019 we use budesonide/formoterol for BRT in asthma at our center in Argentina. The aim was to compare budesonide/formoterol with salbutamol for BRT in stable asthmatic patients that were followed up in a short-acting beta2 agonist (SABA)-free asthma center. METHODS: From the Hospital database, we found for the same patient at least one BRT using salbutamol 200 µg and another with budesonide/formoterol 320/9 µg. RESULTS: We found similar BRT between salbutamol and budesonide/formoterol in 101 asthmatic individuals (26 males) aged 38.14 ± 16.1 yrs (mean ± Standard deviation). The absolute response was 0.18 ± 0.21 L in FEV1 after salbutamol and 0.20 ± 0.22 L in FEV1 after budesonide/formoterol. Afterwards, we showed 202 patients tested with budesonide/formoterol; the mean absolute response was 0.21 ± 0.22 L in FEV1. There were no unexpected safety findings. CONCLUSIONS: In asthmatic patients, we demonstrated similar efficacy between Budesonide/formoterol and salbutamol for BRT.
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Physiology and behavior are synchronized to the external environment by endogenous circadian rhythms that are set to precisely 24 h by exposure to bright light early in the day. Exposure to artificial light outside of the typical solar day, such as during the night, may impair aspects of physiology and behavior in human and non-human animals. Both the intensity and the wavelength of light are important in mediating these effects. The present report is the result of an unplanned change in our vivarium lighting conditions, which led to the observation that dim light during the daytime affects body mass similarly to dim nighttime light exposure in male Swiss Webster mice. Mice exposed to bright days (≥125 lux) with dark nights (0 lux) gained significantly less weight than those exposed to bright days with dim light at night (5 lux) or dim days (≤60 lux) with either dark nights or dim light at night. Notably, among the mice exposed to dim daytime light, no weight gain differences were observed between dark nights and dim light at night exposure; however dim light at night exposure shifted food intake to the inactive phase as previously reported. The mechanisms mediating these effects remain unspecified, but it appears that dimly illuminated days may have similar adverse metabolic effects as exposure to artificial light at night.
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Ritmo Circadiano , Atividade Motora , Masculino , Camundongos , Animais , Ritmo Circadiano/fisiologiaRESUMO
Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce and production, and expanding social life around the clock. However, physiology and behavior that evolved in the context of 24 h solar days are frequently perturbed by exposure to artificial light at night. This is particularly salient in the context of circadian rhythms, the result of endogenous biological clocks with a rhythm of ~24 h. Circadian rhythms govern the temporal features of physiology and behavior, and are set to precisely 24 h primarily by exposure to light during the solar day, though other factors, such as the timing of meals, can also affect circadian rhythms. Circadian rhythms are significantly affected by night shift work because of exposure to nocturnal light, electronic devices, and shifts in the timing of meals. Night shift workers are at increased risk for metabolic disorder, as well as several types of cancer. Others who are exposed to artificial light at night or late mealtimes also show disrupted circadian rhythms and increased metabolic and cardiac disorders. It is imperative to understand how disrupted circadian rhythms alter metabolic function to develop strategies to mitigate their negative effects. In this review, we provide an introduction to circadian rhythms, physiological regulation of homeostasis by the suprachiasmatic nucleus (SCN), and SCN-mediated hormones that display circadian rhythms, including melatonin and glucocorticoids. Next, we discuss circadian-gated physiological processes including sleep and food intake, followed by types of disrupted circadian rhythms and how modern lighting disrupts molecular clock rhythms. Lastly, we identify how disruptions to hormones and metabolism can increase susceptibility to metabolic syndrome and risk for cardiovascular diseases, and discuss various strategies to mitigate the harmful consequences associated with disrupted circadian rhythms on human health.
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Relógios Circadianos , Melatonina , Humanos , Ritmo Circadiano/fisiologia , Núcleo Supraquiasmático/metabolismo , Sono , Melatonina/metabolismo , Ingestão de Alimentos , Relógios Circadianos/fisiologia , LuzRESUMO
INTRODUCTION: Hartmann's procedure (HP) is the conventional treatment in patients with complicated diverticulitis. Segmental resection with primary anastomosis (PA) is a treatment alternative for those patients. Our aim was to compare the postoperative results of HP and PA in patients with complicated diverticulitis (Hinchey stage III). METHODS: A case-control study was conducted on patients operated on for purulent Hinchey stage III diverticulitis, within the time frame of 2000 and 2019. RESULTS: Twenty-seven patients that underwent PA were compared with 27 that underwent HP. The patients that underwent HP had a greater probability of morbidity at 30 days (OR 3.5; 95% CI 1.13-11.25), as well as a greater probability of major complications (OR 10.9; 95% CI 1.26-95.05). CONCLUSION: The patients that underwent segmental resection and PA presented with lower morbidity rates and higher stoma reversal rates than the patients that underwent HP.
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Doença Diverticular do Colo , Diverticulite , Perfuração Intestinal , Humanos , Doença Diverticular do Colo/cirurgia , Doença Diverticular do Colo/complicações , Estudos de Casos e Controles , Perfuração Intestinal/etiologia , Diverticulite/cirurgia , Diverticulite/complicações , Anastomose Cirúrgica/efeitos adversosRESUMO
Circadian rhythms are endogenous biological cycles that regulate physiology and behavior for optimal adaptive function and survival; they are synchronized to precisely 24 hours by daily light exposure. Disruption of the daily light-dark (LD) cycle by exposure to artificial light at night (ALAN) dysregulates core clock genes and biological function. Exposure to ALAN has been associated with increased health risks in humans, and elderly individuals are at elevated risk for poor outcome from disease and often experience elevated exposure to ALAN due to increased care requirements. The role of disrupted circadian rhythms in healthy, aged animals remains unspecified; thus, we hypothesized that disrupted circadian rhythms via chronic exposure to dim ALAN (dLAN) impair immune response and survival in aged mice. Twenty-month-old C57BL/6 male and female mice were exposed to 24 weeks of LD conditions or dLAN (5 lux); then, cell-mediated immune response was assessed using a delayed-type hypersensitivity test. Aged female mice exposed to dLAN displayed dysregulated hypersensitivity and inflammation as a measure of cell-mediated immune response and decreased lifespan compared to females housed in dark nights. Nighttime lighting did not affect cell-mediated immune response or lifespan in males but dysregulated body mass and increased adrenal mass after immune challenge after chronic exposure to dLAN. Together, these data indicate that chronic exposure to dLAN affects lifespan in aged females and suggest that females are more susceptible to the detrimental consequences of disrupted circadian rhythms.
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Ritmo Circadiano , Luz , Humanos , Camundongos , Masculino , Feminino , Animais , Idoso , Lactente , Ritmo Circadiano/fisiologia , Longevidade , Camundongos Endogâmicos C57BL , Fotoperíodo , ImunidadeRESUMO
INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Alemtuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , EspanhaRESUMO
Overreliance on short-acting ß2-agonists (SABA) has been a common feature of asthma management globally for at least 30 years. However, given the evidence against the long-term use of SABA, including potentially increased risk of exacerbations, emergency room visits, overall healthcare resource utilization, and mortality, the latest Global Initiative for Asthma report no longer recommends SABA only therapy. Since 2014, we implemented an ICS-containing reliever strategy at our asthma center at the G Baigorria Hospital in Argentina; we only administered budesonide/formoterol via a single inhaler device across the spectrum of asthma severity and completely eliminated the use of SABA therapy. In this article, we compare hospitalization data from our center, previously reported in the EAGLE study (when inhaled corticosteroids plus as-needed SABA was administered) for the years 1999 and 2004 with data from 2017 to 2018 (when budesonide/formoterol in a single inhaler device was administered as maintenance and/or anti-inflammatory reliever therapy [MART/AIR] without any SABA) from our center, to assess the impact of two distinct asthma management strategies on asthma-related hospitalizations. MART/AIR regimens in our SABA-free center reduced asthma hospitalizations from 9 (1999 and 2004) to 1 (2017 and 2018) (Fisher's exact test, p = 0.031; odds ratio = 0.11; 95% confidence interval [CI] = 0.013-0.98); the hospitalization rate was reduced by 92% (1.47% in 1999 and 2004 to 0.12% in 2017 and 2018). Our data provide preliminary real-world evidence that MART/AIR with budesonide/formoterol simultaneously with SABA elimination across asthma severities is an effective asthma management strategy for reducing asthma-related hospitalizations.
RESUMO
INTRODUCTION AND AIM: Intussusception is rare in adults and can occur in the small bowel and colon. Its atypical presentation makes the diagnosis difficult. The aim of the present study was to evaluate the causes, clinical characteristics, and treatment outcomes of adult intussusception and to determine whether there was an association between etiology and clinical presentation. MATERIALS AND METHODS: A retrospective study was carried out on patients above 18 years of age that were treated for intussusception at a tertiary care hospital, between 2000 and 2020. The findings were summarized utilizing descriptive and inferential statistics. RESULTS: Twenty-eight cases were identified. Median patient age was 46 years (18-80) and median symptom duration was 18 days. Abdominal pain was the most frequent symptom (96.42%). The intussusceptions registered were enteroenteric (14), ileocecal (4), ileocolonic (4), colocolonic (5), and colorrectal (1). Intussusception etiology was benign in 15 cases, 9 were associated with malignancy, and 4 were idiopathic. Surgery was performed on 11 patients with enteroenteric intussusception and on all the cases of ileocecal, ileocolonic, colocolonic, and colorectal intussusception. There were 2 events of perioperative mortality (8%) and 8 of postoperative morbidity (32%). No significant differences were found regarding symptom duration or length of hospital stay, when the etiologic groups were compared. CONCLUSIONS: Intussusception is rare in adults. Diagnosis is a challenge because of the nonspecific signs and symptoms. Surgical resection should be considered in the definitive treatment and management should be individualized according to the patient's comorbidities, clinical presentation, and risk of malignancy.