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Background: Impulse oscillometry (IOs) is a technique used to evaluate lung function that uses sound waves imposed over tidal breathing to characterize the airways and lung parenchyma. IOs has been particularly useful in the identification of obstructive lung defects. The present analysis seeks to explore the use of IOs in the identification of restrictive lung physiology among a group of Gulf War I veterans exposed to depleted uranium (DU). Methods: A total of 36 out of a dynamic 85-veteran cohort attended in-person surveillance visits in 2019 and completed both IOs and PFTs. Performance on IOs was evaluated in a cross-sectional analysis of the group overall and in those identified as having restrictive lung defects defined by either spirometry (FEV1/FVC ≥ LLN and FVC < LLN) or lung volumes (TLC < LLN). Results: A total of 6 individuals were identified as having restriction (4 based on spirometry alone and an additional 2 by lung volumes). When restriction was present, IOs values of both resistance and reactance were significantly more abnormal. Conclusion: In the assessment of lung function, IOs may be advantageous over PFTs because it is faster to perform and effort-independent. Although little is known about the utility of IOs in identifying restrictive lung physiology, our results support its use.
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Acute eosinophilic pneumonia (AEP) is a rare cause of acute respiratory failure. Clinical presentations can range from dyspnoea, fever and cough, to rapidly progressive and potentially fulminant respiratory failure. While its exact cause is often unknown, associations with inhalational injuries and exposures to new medications have been described.We report a case of a middle-aged, non-smoking man with a history of alcohol use disorder. He presented with 4 days of shortness of breath that started hours after taking injectable naltrexone (Vivitrol). The patient had rapidly worsening hypoxaemia, necessitating emergent bronchoscopy with transbronchial biopsies and bronchoalveolar lavage which showed 66% eosinophils. The patient was intubated for the procedure and unable to get extubated due to worsening hypoxaemic respiratory failure with high fractional inspired oxygen requirements. Chest radiograph showed worsening lung infiltrates and with a high index of suspicion for AEP, he was started empirically on methylprednisolone. He had rapid improvement in his respiratory status and was extubated on day 5 of admission then discharged on day 8. Histopathological examination confirmed acute/subacute eosinophilic pneumonia. A 3-week post-discharge follow-up chest radiograph confirmed the full resolution of pulmonary infiltrates.Naltrexone-induced AEP is rare, with only six other cases reported in the literature. Careful history taking and prompt evaluation for AEP are important given the potential for rapid progression to acute hypoxic respiratory failure and the excellent response to steroid treatment.
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Naltrexona , Eosinofilia Pulmonar , Humanos , Masculino , Eosinofilia Pulmonar/induzido quimicamente , Eosinofilia Pulmonar/diagnóstico , Naltrexona/uso terapêutico , Naltrexona/efeitos adversos , Pessoa de Meia-Idade , Antagonistas de Entorpecentes/uso terapêutico , Antagonistas de Entorpecentes/efeitos adversos , Antagonistas de Entorpecentes/administração & dosagem , Metilprednisolona/uso terapêutico , Insuficiência Respiratória/induzido quimicamente , Broncoscopia , Doença Aguda , DispneiaRESUMO
OBJECTIVE: Adverse respiratory outcomes in post-9/11 veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals. METHODS: Veterans completed questionnaires, underwent pulmonary physiology tests (pulmonary function and oscillometry), and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses, and physiology measures were compared in veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. RESULTS: Among 402 study participants, 24% had elevated urine metals, often just exceeding upper limits of reference values. Compared to veterans without elevated metals, those with elevated metals had had higher FEV 1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. CONCLUSIONS: Mild systemic metal elevations in post-9/11 veterans are not associated with adverse respiratory health outcomes.
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Sistema de Registros , Ataques Terroristas de 11 de Setembro , Veteranos , Humanos , Masculino , Pessoa de Meia-Idade , Veteranos/estatística & dados numéricos , Feminino , Estados Unidos , Idoso , United States Department of Veterans Affairs , Metais/urina , Adulto , Testes de Função Respiratória , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Severe hemorrhage is an uncommon yet potentially life-threatening complication of transbronchial lung biopsy. Lung transplantation recipients undergo multiple bronchoscopies with biopsy and are considered to be at an increased risk for bleeding from transbronchial biopsy, independent of traditional risk factors. We aimed to evaluate the efficacy and safety of endobronchial administration of prophylactic topical epinephrine in attenuating transbronchial biopsy-related hemorrhage in lung transplant recipients. METHODS: The Prophylactic Epinephrine for the Prevention of Transbronchial Lung Biopsy-related Bleeding in Lung Transplant Recipients study was a 2-center, randomized, double blind, placebo-controlled clinical trial. Participants undergoing transbronchial lung biopsy were randomized to receive 1:10,000-diluted topical epinephrine vs saline placebo administered prophylactically into the target segmental airway. Bleeding was graded based on a clinical severity scale. The primary efficacy outcome was incidence of severe or very severe hemorrhage. The primary safety outcome was a composite of 3-hours all-cause mortality and an acute cardiovascular event. RESULTS: A total of 66 lung transplantation recipients underwent 100 bronchoscopies during the study period. The primary outcome of severe or very severe hemorrhage occurred in 4 cases (8%) in the prophylactic epinephrine group and in 13 cases (24%) in the control group (p = 0.04). The composite primary safety outcome did not occur in any of the study groups. CONCLUSIONS: In lung transplantation recipients undergoing transbronchial lung biopsy, prophylactic administration of 1:10,000-diluted topical epinephrine into the target segmental airway before biopsy attenuates the incidence of significant endobronchial hemorrhage without conveying a significant cardiovascular risk. (ClinicalTrials.gov identifier: NCT03126968).
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Transplante de Pulmão , Humanos , Transplante de Pulmão/efeitos adversos , Biópsia/métodos , Hemorragia/etiologia , Hemorragia/prevenção & controle , Hemorragia/patologia , Pulmão/patologia , Epinefrina/uso terapêutico , BroncoscopiaRESUMO
OBJECTIVE: Insufficient and disturbed sleep are associated with significant morbidity among working-age adults. Poor sleep results in negative health outcomes and increases economic costs to employers. The current systematic review surveyed the peer-reviewed scientific literature and aggregated scientific evidence of sleep-related economic burdens borne by employers. METHODS: A systematic review was performed to identify peer-reviewed, English language studies evaluating the economic impact of insufficient and disturbed sleep among adult employee populations. An exhaustive literature search was performed using keywords related to sleep, economics, and the workplace. Included were scientific studies (randomized controlled trials, cohort and case control studies, cross-sectional and longitudinal studies) examining specific employee populations with relevant sleep and economic outcomes. Each included study was evaluated for risk of bias and relevant data was extracted and summarized. RESULTS: Sleep problems among employee populations are associated with worsened workplace outcomes, such as presenteeism, absenteeism, and accidents. Sleep problems also increased costs to employers, ranging from US$322 to US$1967 per employee. Interventions to improve sleep, such as the use of blue-light filtering glasses, strategic shift scheduling, and targeted interventions to treat insomnia, may improve workplace outcomes and reduce costs. CONCLUSIONS: This review synthesizes the existing data regarding the negative impacts of insufficient and disturbed sleep on the workplace, suggesting that employers have an economic stake in their employees' sleep. TRIAL REGISTRATION: PROSPERO: CRD42021224212.
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Transtornos do Sono-Vigília , Local de Trabalho , Adulto , Humanos , Estudos Transversais , Inquéritos e Questionários , Sono , AbsenteísmoRESUMO
BACKGROUND: Blast lung overpressure has received interest as a cause of chronic respiratory disease in Service members who deployed in support of U.S. military operations in Southwest Asia and Afghanistan since 2001. We studied whether veterans who experienced blast exposure report more chronic respiratory symptoms and diagnoses compared to deployed veterans who did not. METHODS: 9,000 veterans included in the Department of Veterans Affairs Toxic Embedded Fragment Registry were invited to complete a survey assessing chronic respiratory symptoms, diagnoses, and exposures. Blast exposure was assessed using the Brief Traumatic Brain Injury Screen and by presence of other symptoms such as blast-induced loss of consciousness. RESULTS: Participants (n = 2147) were predominantly <40 years old, served in the Army, and injured on average 12.8 years previously. 91% reported blast exposure. Blast-exposed veterans were significantly more likely to report cough (OR 1.8), wheeze (OR 2.4), and dyspnea (OR 1.8), even after adjustment for covariates including smoking and occupational exposures to dust, fume, and gas. Veterans reporting higher severity of blast impact, such as traumatic brain injury or loss of consciousness, were more likely to report cough, wheeze, or dyspnea. Veterans with higher severity of blast impact by multiple measures were also more likely to report having COPD. Those reporting a physician-diagnosis of traumatic brain injury were significantly more likely to report having both asthma (OR 1.5) and COPD (OR 1.5). CONCLUSIONS: Blast exposure is associated with respiratory symptoms and COPD. Respiratory system evaluation may warrant inclusion as a standard part of barotrauma health assessment.
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Traumatismos por Explosões , Lesões Encefálicas Traumáticas , Doença Pulmonar Obstrutiva Crônica , Transtornos de Estresse Pós-Traumáticos , Veteranos , Adulto , Campanha Afegã de 2001- , Traumatismos por Explosões/complicações , Traumatismos por Explosões/diagnóstico , Traumatismos por Explosões/epidemiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/etiologia , Tosse/complicações , Poeira , Dispneia/complicações , Humanos , Guerra do Iraque 2003-2011 , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sistema Respiratório , Autorrelato , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inconsciência/complicaçõesRESUMO
Brainstem strokes can present with an array of ophthalmologic findings depending on the location of the lesion. Eye movements are recorded on electrooculogram during polysomnography for sleep staging. We present the case of a patient with a dorsal midbrain hemorrhagic stroke and nystagmus with distinct findings on the electrooculogram during polysomnography. These eye movements from nystagmus differed in many aspects (frequency and amplitude) from the classic findings of other eye movements recorded during different stages of sleep. These polysomnography findings have not been reported in the setting of midbrain stroke. Future studies comparing nystagmus in multiple sleep stages in stroke patients would be of interest. CITATION: Shoukat U, Glick DR, Chaturvedi S, Diaz-Abad M. Images: Polysomnographic findings of nystagmus caused by a midbrain hemorrhagic stroke. J Clin Sleep Med. 2022;18(5):1479-1482.
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Acidente Vascular Cerebral Hemorrágico , Humanos , Mesencéfalo/diagnóstico por imagem , Polissonografia , Sono , Fases do SonoRESUMO
ABSTRACT: Gulf War I veterans who were victims of depleted uranium (DU) "friendly-fire" incidents have undergone longitudinal health surveillance since 1994. During the spring of 2019, 36 members of the cohort were evaluated with a monitoring protocol including exposure assessment for total and isotopic uranium concentrations in urine and a comprehensive review of health outcomes, including measures of bone metabolism and bone mineral density (BMD) determination. Elevated urine U concentrations were observed in cohort members with retained depleted uranium (DU) shrapnel fragments. In addition, a measure of bone resorption, N-telopeptide, showed a statistically significant increase in those in the high DU subgroup, a finding consistent with a statistically significant decrease in bone mass also observed in this high DU subgroup compared to the low DU subgroup. After more than 25 y since first exposure to DU, an aging cohort of military veterans continues to show few U-related health effects in known target organs of U toxicity. The new finding of impaired BMD in the high DU subgroup has now been detected in two consecutive surveillance visits. While this is a biologically plausible uranium effect, it is not reflected in other measures of bone metabolism in the full cohort, which have largely been within normal limits. However, ongoing accrual of the U burden from fragment absorption over time and the effect of aging further impairing BMD suggest the need for future surveillance assessments of this cohort.
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Exposição Ocupacional , Urânio , Veteranos , Osso e Ossos , Guerra do Golfo , Humanos , Exposição Ocupacional/análise , Urânio/efeitos adversos , Urânio/urinaRESUMO
The coronavirus severe acute respiratory syndrome (COVID-19) pandemic has placed increased stress on healthcare workers (HCWs). While anxiety and post-traumatic stress have been evaluated in HCWs during previous pandemics, moral injury, a construct historically evaluated in military populations, has not. We hypothesized that the experience of moral injury and psychiatric distress among HCWs would increase over time during the pandemic and vary with resiliency factors. From a convenience sample, we performed an email-based, longitudinal survey of HCWs at a tertiary care hospital between March and July 2020. Surveys measured occupational and resilience factors and psychiatric distress and moral injury, assessed by the Impact of Events Scale-Revised and the Moral Injury Events Scale, respectively. Responses were assessed at baseline, 1-month, and 3-month time points. Moral injury remained stable over three months, while distress declined. A supportive workplace environment was related to lower moral injury whereas a stressful, less supportive environment was associated with increased moral injury. Distress was not affected by any baseline occupational or resiliency factors, though poor sleep at baseline predicted more distress. Overall, our data suggest that attention to improving workplace support and lowering workplace stress may protect HCWs from adverse emotional outcomes.
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COVID-19/psicologia , Pessoal de Saúde/psicologia , Princípios Morais , Angústia Psicológica , Resiliência Psicológica , Humanos , Estudos Longitudinais , Estresse Ocupacional/psicologia , Pandemias , Apoio Social , Local de TrabalhoRESUMO
Rheumatoid arthritis (RA) is a common autoimmune disease most well-known for its inflammatory, destructive polyarthropathy. Extraarticular manifestations of the disease may involve the respiratory system, including interstitial lung disease, pleural disease, pulmonary vascular abnormalities, and airways disease. Smoking is highly prevalent in the RA population, and may even have a synergistic effect in disease development and progression. In the diagnosis of pulmonary disease, this presents a unique diagnostic and therapeutic challenge. We present a case of a woman in her 50s who presented for evaluation of dyspnea and was found to have obstructive lung disease. In addition to RA, she had a significant smoking history and also owned pet birds, making definitive diagnosis difficult. Ultimately, chest imaging was crucial in identifying RA-related lung disease as the root cause of her symptoms, leading to successful treatment and symptom management.
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OBJECTIVE: Gulf War I (GWI) Veterans exposed to depleted uranium (DU) have undergone biennial surveillance to assess for DU-related health effects. No DU-specific respiratory effects have been observed cross-sectionally, but longitudinal lung function decline has not been assessed. METHODS: A dynamic cohort of 71 Veterans underwent spirometry testing between 1999 and 2019. Longitudinal rates of decline of spirometry values were compared among Veterans with high versus low uranium levels using a linear mixed model. RESULTS: There was no significant difference in rate of decline of spirometry values between Veterans with high versus low uranium levels. The overall rate of decline was similar to that of the general population. CONCLUSIONS: In 20 years of follow-up, there does not appear to be an accelerated rate of decline of lung function among veterans exposed to depleted uranium.
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Exposição Ocupacional , Síndrome do Golfo Pérsico , Urânio , Veteranos , Guerra do Golfo , Humanos , Pulmão , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Síndrome do Golfo Pérsico/induzido quimicamente , Síndrome do Golfo Pérsico/epidemiologia , Urânio/toxicidadeAssuntos
Centros Médicos Acadêmicos , Algoritmos , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/diagnóstico , Sistemas de Apoio a Decisões Clínicas/estatística & dados numéricos , Testes Diagnósticos de Rotina/normas , Registros Eletrônicos de Saúde/estatística & dados numéricos , Melhoria de Qualidade , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVES: Anticipatory grief, the experience of grief before the death of a mourned individual, is common among people with seriously ill loved ones and associated with impaired social problem solving. We sought to evaluate anticipatory grief in the Intensive Care Unit setting. RESEARCH METHODOLOGY/DESIGN: Cross-sectional study of surrogate decision-makers of patients admitted to an intensive care unit, incorporating survey methodology. SETTING: Intensive care units at a tertiary care centre. MAIN OUTCOME MEASURES: Surrogates completed a 78-question, self-administered questionnaire consisting of demographic and clinical data, as well as three validated instruments: Anticipatory Grief Scale (AGS), Hospital Anxiety and Depression Scale (HADS), and Social Problem Solving Inventory Revised Short Form (SPSI-R:S). MAIN RESULTS: Surveys were completed by 50 surrogate decision-makers, among whom anticipatory grief was elevated and associated with anxiety and depression. Anticipatory grief was also significantly associated with worsened overall problem solving (Spearman's Rho -0.32, p value 0.02). Surrogates with loved ones who were older or admitted to a trauma unit experienced anticipatory grief at lower levels. Prior admission and Charlson Comorbidity Index scores were not associated with anticipatory grief. CONCLUSION: Levels of anticipatory grief in the intensive care unit are high and associated with concurrent anxiety and depression. Association of anticipatory grief with worsened social problem solving may worsen decision making ability in surrogates.
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Antecipação Psicológica , Cuidadores/psicologia , Estado Terminal/psicologia , Tomada de Decisões , Pesar , Adulto , Idoso , Enfermagem de Cuidados Críticos , Estado Terminal/enfermagem , Estudos Transversais , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Maryland , Pessoa de Meia-Idade , Psicometria , Inquéritos e QuestionáriosRESUMO
We have developed and tested two linked but separable structured inquiry exercises using a set of Drosophila melanogaster GAL4 enhancer trap strains for an upper-level undergraduate laboratory methods course at Bucknell University. In the first, students learn to perform inverse PCR to identify the genomic location of the GAL4 insertion, using FlyBase to identify flanking sequences and the primary literature to synthesize current knowledge regarding the nearest gene. In the second, we cross each GAL4 strain to a UAS-CD8-GFP reporter strain, and students perform whole mount CNS dissection, immunohistochemistry, confocal imaging, and analysis of developmental expression patterns. We have found these exercises to be very effective in teaching the uses and limitations of PCR and antibody-based techniques as well as critical reading of the primary literature and scientific writing. Students appreciate the opportunity to apply what they learn by generating novel data of use to the wider research community.
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Currículo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Elementos Facilitadores Genéticos , Laboratórios , Aprendizagem , Fatores de Transcrição/genética , Universidades , Animais , Sequência de Bases , Encéfalo/metabolismo , Regulação da Expressão Gênica , Genes de Insetos , Dados de Sequência Molecular , Corpos Pedunculados/metabolismo , Reação em Cadeia da PolimeraseRESUMO
Two defining characteristics of stem cells are their multilineage differentiation potential (multipotency or pluripotency) and their capacity for self-renewal. Growth factors are well-established regulators of stem cell differentiation and self renewal, but less is known about the influence of the metabolic state on stem cell function. Recent studies investigating cellular metabolism during the differentiation of adult stem cells, human embryonic stem cells (ESCs), and induced pluripotent stem cells have demonstrated that activation of specific metabolic pathways depends on the type of stem cells as well as the lineage cells are differentiating into and that these metabolic pathways can influence the differentiation process. However, some common patterns have emerged, suggesting that undifferentiated stem cells primarily rely on glycolysis to meet energy demands. Our own data indicate that undifferentiated ESCs not only exhibit a low mitochondrial membrane potential but also express high levels of the mitochondrial uncoupling protein 2 and of glutamine metabolism regulators when compared with differentiated cells. More importantly, interventions that target stem cell metabolism are able to either prevent or enhance differentiation. These findings suggest that the metabolic state of stem cells is not just a marker of their differentiation status but also plays an active role in regulating stem cell function. Regulatory metabolic pathways in stem cells may thus serve as important checkpoints that can be modulated to direct the regenerative capacity of stem cells.
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OBJECTIVES: This study sought to determine whether the combined trajectories of cardiac biomarkers identify those older adults with initial low levels who have an increased risk for structural heart disease, incident heart failure (HF), and cardiovascular (CV) death. BACKGROUND: Initial low levels of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) identify older adults at lower risk for CV events. METHODS: We performed an observational study among older adults without prevalent HF in the CHS (Cardiovascular Health Study). NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years. In those with low baseline levels, a significant increase was defined as cardiac troponin T (cTnT) >50% and NT-proBNP >25% increase to >190 pg/ml. Left ventricular ejection fraction and left ventricular mass were measured by echocardiography at baseline and 5 years. Cox regression was used to estimate the association of change in biomarkers with HF and CV mortality. RESULTS: Among 2,008 participants with initially low biomarker concentrations, significant increases occurred in 14.8% for cTnT only, 13.2% for NT-proBNP only, and 6.1% for both. After 10 years, cumulative HF incidence was 50.4% versus 12.2% among those with both biomarkers versus neither biomarker increased. The adjusted relative risk comparing those with increases in both biomarkers versus neither biomarker was 3.56 for incident HF (95% confidence interval: 2.56 to 4.97) and 2.98 for CV mortality (95% confidence interval: 2.98 to 4.26). Among 1,340 participants with serial echocardiography, the frequency of new abnormal left ventricular ejection fraction was 11.8% versus 4% for those with increases in both biomarkers versus neither biomarker (p = 0.007). CONCLUSIONS: Among older adults without HF with initially low cTnT and NT-proBNP, the long-term trajectory of both biomarkers predicts systolic dysfunction, incident HF, and CV death.
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Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Ventrículos do Coração/patologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina T/sangue , Idoso , Biomarcadores/sangue , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Estudos Prospectivos , Medição de Risco , Fatores de Tempo , UltrassonografiaRESUMO
BNip3 localizes to the outer mitochondrial membrane, where it functions in mitophagy and mitochondrial dynamics. While the BNip3 protein is constitutively expressed in adult liver from fed mice, we have shown that its expression is superinduced by fasting of mice, consistent with a role in responses to nutrient deprivation. Loss of BNip3 resulted in increased lipid synthesis in the liver that was associated with elevated ATP levels, reduced AMP-regulated kinase (AMPK) activity, and increased expression of lipogenic enzymes. Conversely, there was reduced ß-oxidation of fatty acids in BNip3 null liver and also defective glucose output under fasting conditions. These metabolic defects in BNip3 null liver were linked to increased mitochondrial mass and increased hepatocellular respiration in the presence of glucose. However, despite elevated mitochondrial mass, an increased proportion of mitochondria exhibited loss of mitochondrial membrane potential, abnormal structure, and reduced oxygen consumption. Elevated reactive oxygen species, inflammation, and features of steatohepatitis were also observed in the livers of BNip3 null mice. These results identify a role for BNip3 in limiting mitochondrial mass and maintaining mitochondrial integrity in the liver that has consequences for lipid metabolism and disease.
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Metabolismo dos Lipídeos , Proteínas de Membrana/metabolismo , Mitocôndrias Hepáticas/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Células Cultivadas , Jejum/metabolismo , Ácidos Graxos/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Gluconeogênese , Glucose/metabolismo , Lipogênese , Masculino , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Mitocondriais/deficiência , Proteínas Mitocondriais/genética , Modelos Biológicos , Oxirredução , Consumo de OxigênioRESUMO
Autophagy is a self-degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Autophagy also plays a housekeeping role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria, endoplasmic reticulum and peroxisomes, as well as eliminating intracellular pathogens. Thus, autophagy is generally thought of as a survival mechanism, although its deregulation has been linked to non-apoptotic cell death. Autophagy can be either non-selective or selective in the removal of specific organelles, ribosomes and protein aggregates, although the mechanisms regulating aspects of selective autophagy are not fully worked out. In addition to elimination of intracellular aggregates and damaged organelles, autophagy promotes cellular senescence and cell surface antigen presentation, protects against genome instability and prevents necrosis, giving it a key role in preventing diseases such as cancer, neurodegeneration, cardiomyopathy, diabetes, liver disease, autoimmune diseases and infections. This review summarizes the most up-to-date findings on how autophagy is executed and regulated at the molecular level and how its disruption can lead to disease.