Decoding allosteric regulation by the acyl carrier protein.

Enzymes in multistep metabolic pathways utilize an array of regulatory mechanisms to maintain a delicate homeostasis [K. Magnuson, S. Jackowski, C. O. Rock, J. E. Cronan, Jr, Microbiol. Rev. 57, 522-542 (1993)]. Carrier proteins in particular play an essential role in shuttling substrates between appropriate enzymes in metabolic pathways. Although hypothesized [E. Ploskon et al., Chem. Biol. 17, 776-785 (2010)], allosteric regulation of substrate delivery has never before been demonstrated for any acyl carrier protein (ACP)-dependent pathway. Studying these mechanisms has remained challenging due to the transient and dynamic nature of protein-protein interactions, the vast diversity of substrates, and substrate instability [K. Finzel, D. J. Lee, M. D. Burkart, ChemBioChem 16, 528-547 (2015)]. Here we demonstrate a unique communication mechanism between the ACP and partner enzymes using solution NMR spectroscopy and molecular dynamics to elucidate allostery that is dependent on fatty acid chain length. We demonstrate that partner enzymes can allosterically distinguish between chain lengths via protein-protein interactions as structural features of substrate sequestration are translated from within the ACP four-helical bundle to the protein surface, without the need for stochastic chain flipping. These results illuminate details of cargo communication by the ACP that can serve as a foundation for engineering carrier protein-dependent pathways for specific, desired products.

Field testing Australian bat lyssavirus risk communication resources.

ISSUE ADDRESSED: Australian bat lyssavirus (ABLV) is a fatal zoonosis, which can be transmitted to humans through scratches or bites from infected bats. Currently, there is a lack of research evaluating risk communication resources about ABLV or the dangers from handling bats. The purpose of this study was to field test resources aimed at educating the public about risks to humans and bats from human-bat interaction, then update these resources based upon feedback to ensure they were relevant and appropriately targeted to the public. METHODS: Thirteen semi-structured interviews with a purposive sample of participants chosen for maximum variation of age and sex were conducted. Two investigators analysed the data independently using a deductive approach and then came to consensus by discussion. RESULTS: The main themes were a wide-ranging level of knowledge and opinions about bats, the resources having an effect on people, and messaging in relation to children and pets being particularly important. CONCLUSION: This study highlighted the complexities of risk communication to a broad audience with varied experience and knowledge about bats, and the importance of evaluation prior to implementation to ensure risk communication is relevant and appealing to the intended audience. SO WHAT?: Field testing of health education material prior to implementation is an effective way to ensure key messages are understood, and is important when communicating about fatal but preventable zoonoses such as ABLV.

Combating ageism in medical education with narrative medicine.

Ageism is common in medical trainees and difficult to overcome. The My Life, My Story program has been shown to be an effective tool for increasing empathy. We explored its use as an instrument for combating ageism by implementing it in a Geriatrics clerkship for fourth year medical students. During our evaluation, 151 students interviewed patients about their lives using a semi-structured question guide. Students completed the UCLA Geriatrics Attitudes Scale and the Expectations Regarding Aging Survey pre-and post-clerkship. We also facilitated 9 student debriefs and 5 faculty interviews. After completing My Life, My Story, students were more likely to disagree with "I would rather see younger patients than elderly ones" and "it's normal to be depressed when you are old". In qualitative analysis of the debriefs, we identified a key summative theme: "impact of the intervention on care teams". Within that, we describe three subthemes: an awareness of richness of the lives led by older people, their current value to society, and the social determinants of health they have faced. After participating in My Life, My Story, students' attitudes toward aging changed. A narrative medicine program using life stories can be a practical tool for addressing ageist stereotypes.

Human influence has intensified extreme precipitation in North America.

Precipitation extremes have implications for many facets of both the human and natural systems, predominantly through flooding events. Observations have demonstrated increasing trends in extreme precipitation in North America, and models and theory consistently suggest continued increases with future warming. Here, we address the question of whether observed changes in annual maximum 1- and 5-d precipitation can be attributed to human influence on the climate. Although attribution has been demonstrated for global and hemispheric scales, there are few results for continental and subcontinental scales. We utilize three large ensembles, including simulations from both a fully coupled Earth system model and a regional climate model. We use two different attribution approaches and find many qualitatively consistent results across different methods, different models, and different regional scales. We conclude that external forcing, dominated by human influence, has contributed to the increase in frequency and intensity of regional precipitation extremes in North America. If human emissions continue to increase, North America will see further increases in these extremes.

Positive Minds for Refugees: A Qualitative Study to Inform Intervention Development.

Refugees face significantly worse mental health outcomes compared to the general population within their host country; however, few refugee-specific mental health programs exist within the United States. Utilizing Community-based Participatory Research methods, a community-based mental health intervention named Positive Minds for Refugees (PMR) is in development. In this preliminary study, we shared the in-development intervention with refugees (n = 8), holding a series of 3 focus groups to gain feedback on the intervention content and determine acceptability. Findings suggest that the intervention is generally acceptable and relevant to the refugee community. Mental health for refugees is closely linked with their ability to navigate new social, cultural, and physical environments during resettlement; therefore, to address unmet needs, additional content should be added on: American cultural norms, navigating US society, and coping with social isolation and self-care. This study highlights cultural considerations for presenting written intervention content and implementing sessions.

Control of Unsaturation in De Novo Fatty Acid Biosynthesis by FabA.

Carrier protein-dependent biosynthesis provides a thiotemplated format for the production of natural products. Within these pathways, many reactions display exquisite substrate selectivity, a regulatory framework proposed to be controlled by protein-protein interactions (PPIs). In Escherichia coli, unsaturated fatty acids are generated within the de novo fatty acid synthase by a chain length-specific interaction between the acyl carrier protein AcpP and the isomerizing dehydratase FabA. To evaluate PPI-based control of reactivity, interactions of FabA with AcpP bearing multiple sequestered substrates were analyzed through NMR titration and guided high-resolution docking. Through a combination of quantitative binding constants, residue-specific perturbation analysis, and high-resolution docking, a model for substrate control via PPIs has been developed. The in silico results illuminate the mechanism of FabA substrate selectivity and provide a structural rationale with atomic detail. Helix III positioning in AcpP communicates sequestered chain length identity recognized by FabA, demonstrating a powerful strategy to regulate activity by allosteric control. These studies broadly illuminate carrier protein-dependent pathways and offer an important consideration for future inhibitor design and pathway engineering.

Glucocorticoids enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia.

FLT3 is a frequently mutated gene that is highly associated with a poor prognosis in acute myeloid leukemia (AML). Despite initially responding to FLT3 inhibitors, most patients eventually relapse with drug resistance. The mechanism by which resistance arises and the initial response to drug treatment that promotes cell survival is unknown. Recent studies show that a transiently maintained subpopulation of drug-sensitive cells, so-called drug-tolerant "persisters" (DTPs), can survive cytotoxic drug exposure despite lacking resistance-conferring mutations. Using RNA sequencing and drug screening, we find that treatment of FLT3 internal tandem duplication AML cells with quizartinib, a selective FLT3 inhibitor, upregulates inflammatory genes in DTPs and thereby confers susceptibility to anti-inflammatory glucocorticoids (GCs). Mechanistically, the combination of FLT3 inhibitors and GCs enhances cell death of FLT3 mutant, but not wild-type, cells through GC-receptor-dependent upregulation of the proapoptotic protein BIM and proteasomal degradation of the antiapoptotic protein MCL-1. Moreover, the enhanced antileukemic activity by quizartinib and dexamethasone combination has been validated using primary AML patient samples and xenograft mouse models. Collectively, our study indicates that the combination of FLT3 inhibitors and GCs has the potential to eliminate DTPs and therefore prevent minimal residual disease, mutational drug resistance, and relapse in FLT3-mutant AML.

Comparative chemical genomic profiling across plant-based hydrolysate toxins reveals widespread antagonism in fitness contributions.

The budding yeast Saccharomyces cerevisiae has been used extensively in fermentative industrial processes, including biofuel production from sustainable plant-based hydrolysates. Myriad toxins and stressors found in hydrolysates inhibit microbial metabolism and product formation. Overcoming these stresses requires mitigation strategies that include strain engineering. To identify shared and divergent mechanisms of toxicity and to implicate gene targets for genetic engineering, we used a chemical genomic approach to study fitness effects across a library of S. cerevisiae deletion mutants cultured anaerobically in dozens of individual compounds found in different types of hydrolysates. Relationships in chemical genomic profiles identified classes of toxins that provoked similar cellular responses, spanning inhibitor relationships that were not expected from chemical classification. Our results also revealed widespread antagonistic effects across inhibitors, such that the same gene deletions were beneficial for surviving some toxins but detrimental for others. This work presents a rich dataset relating gene function to chemical compounds, which both expands our understanding of plant-based hydrolysates and provides a useful resource to identify engineering targets.

Paving the way for universal medical student training in serious illness communication: the Massachusetts Medical Schools' Collaborative.

BACKGROUND: Patients with serious illness look to their clinicians for discussion and guidance on high-stakes treatment decisions, which are complex, emotional and value-laden. However, required training in serious illness communication is rare in U.S. medical schools, with efforts at curricular reform stymied by competing institutional demands, lack of resources and accreditation requirements. We describe an approach to building and scaling medical student training in serious illness communication through the creation of a statewide collaborative of medical schools. METHODS: The Massachusetts Medical Schools' Collaborative is a first-of-its-kind group that promotes longitudinal, developmentally-based curricula in serious illness communication for all students. Convened externally by the Massachusetts Coalition for Serious Illness Care, the collaborative includes faculty, staff, and students from four medical schools. RESULTS: The collaborative started with listening to member's perspectives and collectively developed core competencies in serious illness communication for implementation at each school. We share early lessons on the opportunities, challenges and sustainability of our statewide collective action to influence curricular reform, which can be replicated in other topic areas. CONCLUSIONS: Our next steps include curriculum mapping, student focus groups and faculty development to guide successful and enduring implementation of the competencies to impact undergraduate medical education in Massachusetts and beyond.

The ReFRAME library as a comprehensive drug repurposing library and its application to the treatment of cryptosporidiosis.

The chemical diversity and known safety profiles of drugs previously tested in humans make them a valuable set of compounds to explore potential therapeutic utility in indications outside those originally targeted, especially neglected tropical diseases. This practice of "drug repurposing" has become commonplace in academic and other nonprofit drug-discovery efforts, with the appeal that significantly less time and resources are required to advance a candidate into the clinic. Here, we report a comprehensive open-access, drug repositioning screening set of 12,000 compounds (termed ReFRAME; Repurposing, Focused Rescue, and Accelerated Medchem) that was assembled by combining three widely used commercial drug competitive intelligence databases (Clarivate Integrity, GVK Excelra GoStar, and Citeline Pharmaprojects), together with extensive patent mining of small molecules that have been dosed in humans. To date, 12,000 compounds (∼80% of compounds identified from data mining) have been purchased or synthesized and subsequently plated for screening. To exemplify its utility, this collection was screened against Cryptosporidium spp., a major cause of childhood diarrhea in the developing world, and two active compounds previously tested in humans for other therapeutic indications were identified. Both compounds, VB-201 and a structurally related analog of ASP-7962, were subsequently shown to be efficacious in animal models of Cryptosporidium infection at clinically relevant doses, based on available human doses. In addition, an open-access data portal (https://reframedb.org) has been developed to share ReFRAME screen hits to encourage additional follow-up and maximize the impact of the ReFRAME screening collection.

Posterior Tibial Slope is Increased in Patients With Tibial Tubercle Fractures and Osgood-Schlatter Disease.

BACKGROUND: Osgood-Schlatter disease (OSD) and tibial tubercle fractures are pathologies that affect the tibial tubercle apophysis in preadolescents and adolescents. Anatomic alignment of the proximal tibia may explain why some children develop OSD or sustain tibial tubercle fractures and some do not. Recent data has shown an association between posterior tibial slope angle (PTSA) and both OSD and proximal tibia physeal fractures. In this study, we compare radiographic parameters between patients with non-OSD knee pain, knees with OSD, and knees with tibial tubercle fracture to elucidate a difference between these groups. METHODS: Patients treated for OSD, tibial tubercle fractures, and knee pain, from 2012 to 2018, were retrospectively reviewed. Radiographic parameters for each study group included PTSA, anatomic lateral distal femoral angle, anatomic medial proximal tibial angle, patellar articular height, and the distance from the inferior aspect of the patellar articular surface. Caton-Deschamps index was then calculated. Demographic data was collected including age, sex, and body mass index. Demographic and radiographic data was compared using analysis of variance tests, χ2 tests, 2-sample t tests, and multiple linear regression. RESULTS: Two hundred fifty-one knees in 229 patients met inclusion criteria for the study. In all, 76% were male and the average age of the overall cohort was 14 years old. In patients with tibial tubercle fractures, the majority of fractures were Ogden type 3b (65%). After controlling for demographic variability, average PTSA in the fracture cohort was significantly greater than that in the control cohort (ß=3.49, P<0.001). The OSD cohort had a significantly greater posterior slope (ß=3.14) than the control cohort (P<0.001). There was no statistically significant difference between the fracture and OSD cohorts. There was also no difference in Caton-Deschamps index between the 2 study groups when compared with the control group. CONCLUSION: This study demonstrates that patients with tibial tubercle fractures and patients with OSD have an increased PTSA when compared with the control group. This information adds to the body of evidence that increased tibial slope places the proximal tibial physis under abnormal stress which may contribute to the development of pathologic conditions of proximal tibia such as OSD and tibial tubercle fractures. LEVEL OF EVIDENCE: Level III; retrospective comparative study.

Inhibition of Cardiac RIP3 Mitigates Early Reperfusion Injury and Calcium-Induced Mitochondrial Swelling without Altering Necroptotic Signalling.

Receptor-interacting protein kinase 3 (RIP3) is a convergence point of multiple signalling pathways, including necroptosis, inflammation and oxidative stress; however, it is completely unknown whether it underlies acute myocardial ischemia/reperfusion (I/R) injury. Langendorff-perfused rat hearts subjected to 30 min ischemia followed by 10 min reperfusion exhibited compromised cardiac function which was not abrogated by pharmacological intervention of RIP3 inhibition. An immunoblotting analysis revealed that the detrimental effects of I/R were unlikely mediated by necroptotic cell death, since neither the canonical RIP3-MLKL pathway (mixed lineage kinase-like pseudokinase) nor the proposed non-canonical molecular axes involving CaMKIIδ-mPTP (calcium/calmodulin-dependent protein kinase IIδ-mitochondrial permeability transition pore), PGAM5-Drp1 (phosphoglycerate mutase 5-dynamin-related protein 1) and JNK-BNIP3 (c-Jun N-terminal kinase-BCL2-interacting protein 3) were activated. Similarly, we found no evidence of the involvement of NLRP3 inflammasome signalling (NOD-, LRR- and pyrin domain-containing protein 3) in such injury. RIP3 inhibition prevented the plasma membrane rupture and delayed mPTP opening which was associated with the modulation of xanthin oxidase (XO) and manganese superoxide dismutase (MnSOD). Taken together, this is the first study indicating that RIP3 regulates early reperfusion injury via oxidative stress- and mitochondrial activity-related effects, rather than cell loss due to necroptosis.

The Communication Benefits of Participation in Camp Dream. Speak. Live.: An Extension and Replication.

School-based guidelines often require that treatment focuses on minimizing or eliminating stuttered speech. The purpose of this study was to examine the benefits of explicit training in communication competencies to children who stutter without targeting stuttered speech. Thirty-seven children (ages 4-16) completed Camp Dream. Speak. Live., an intensive group treatment program which targets the psychosocial needs and communication of children who stutter. Outcome measures included the Overall Assessment of the Speaker's Experience of Stuttering (OASES), the Communication Attitude Test for Preschool and Kindergarten Children Who Stutter (KiddyCAT), and the Patient Reported Measurement Information System (PROMIS) Pediatric Peer Relationships Short Form (PROMIS Peer Relationships) and Parent Proxy Peer Relationships Short Form (PROMIS Parent Proxy). Pre- and posttreatment public presentations were rated on nine core verbal and nonverbal communication competencies by a neutral observer. Similar to previous studies, participants demonstrated significant improvements in communication attitudes (OASES) and perceived ability to establish peer relationships (PROMIS Peer Relationships), particularly school-aged participants (ages 7-16). Participants also demonstrated significant improvement in eight of the nine communication competencies. Findings suggest that, in addition to the psychosocial gains of programs such as Camp Dream. Speak. Live., children who stutter benefit from explicit training in communication skills, and these gains are not dependent on the presence of stuttered speech.

Time-resolved FRET and NMR analyses reveal selective binding of peptides containing the LC3-interacting region to ATG8 family proteins.

Selective autophagy sequesters cytoplasmic cargo for lysosomal degradation via the binding of autophagy receptors to Atg8 (autophagy-related 8) family proteins on the autophagic membrane. The sole yeast Atg8 gene has six mAtg8 (mammalian Atg8) homologs, including the MAP1LC3 (microtubule-associated protein-1 light chain 3) family and the GABA receptor-associated proteins. Selective autophagy receptors interact with two conserved hydrophobic pockets (termed the W-site and L-site) of mATG8 proteins through a linear motif called the LC3-interacting region (LIR) with the general composition (W/F/Y)XX(I/L/V). To address a lack in our knowledge regarding LIR peptide specificity toward each mATG8 homolog, here we used competitive time-resolved FRET to sensitively and quantitatively characterize the interactions between LIRs and mAtg8. We report that 14 representative LIR-containing peptides display differential binding affinities toward the mAtg8 proteins and identified the LIR domain peptide of TP53INP1 as exhibiting high affinity for all six mATG8 proteins. Using peptide truncation studies, we found that both N- and C-terminal acidic residues, as well as the C-terminal Cys residue of the TP53INP1 LIR peptide, are required for its high-affinity binding to LC3A and LC3B, whereas binding to the GABARAP subfamily proteins was facilitated by residues either N-terminal or C-terminal to the core motif. Finally, we used NMR chemical shift perturbation analysis to gain molecular insights into these findings. Collectively, our results may aid in the development of molecules that selectively disrupt specific mATG8-LIR interactions to dissect the biological roles of the six mATG8 homologs for potential therapeutic applications.

Clinical experience of intramuscular immunoglobulin for measles prophylaxis in children: Is it practical?

Measles continues to be a public health concern world-wide. Vulnerable individuals including those in which vaccinations is contraindicated, may be reliant on normal human immunoglobulin (NHIG) prophylaxis in an aim to prevent disease. This paper will summarise and discuss a tertiary paediatric hospital's clinical experience and the practicalities of administering intramuscular (IM) NHIG to paediatric patients as per the current measles prophylaxis guidelines in Australia. Following potential exposure within the emergency department, 17 paediatric patients (0-15 years) were recommended IM NHIG for prophylaxis. The dose of NHIG ranged from 0.6 to 15 mL and required multiple (2-8) injections. Two patients required sedation for staff to safely administer the injections. Staff involved with these cases reported administering multiple injections to paediatric patients to be a traumatising experience. They also expressed views that the injection of large volumes via the IM route was an impractical method of administration. Based on this experience, we recommend intravenous immunoglobulin be considered when large volumes of NHIG are recommended intramuscularly.

ECMO as a Platform for Rapid Ammonia Removal in a Neonate with Multienzyme Urea Cycle Disorder.

Since the initial deployment of neonatal extracorporeal membrane oxygenation (ECMO) for respiratory failure, the use of ECMO in this population has diversified. We present a term female infant with carbamoyl phosphate synthetase 1 and partial N-acetylglutamate synthase deficiencies who developed severe hyperammonemia refractory to medical management requiring venoarterial ECMO-driven continuous veno-venous hemodiafiltration for ammonia detoxification. This case report illustrates a subpopulation where neonatal ECMO may improve survival and neurodevelopmental outcomes. To our knowledge, this is the first reported case of a urea cycle defect arising from two proximal enzyme deficiencies. Also, this is one of the few reported patients with UCD associated with peak ammonia levels >2,000 µmol/L who survived to hospital discharge after the successful use of ECMO for ammonia reduction. This case will add to the existing scant literature supporting the use of ECMO as a platform for rapid removal of serum ammonia.

Research: Comparing ASTM F1671 with a Modified Dot-Blot Method to Evaluate Personal Protective Materials.

Effective personal protective equipment (PPE) is critical in preventing the spread of infectious diseases. Appropriate test systems and test soils are needed to adequately evaluate PPE. ASTM test method F903, which specifies the test method setup also used in ASTM F1670 and F1671, has been used for decades to test liquid (ASTM F1670) or viral (ASTM F1671) penetration resistance of PPE fabrics. However, an alteration of the bacteriophage propagation method detailed in the standard was necessary to obtain consistent titers of virus. In this study, modification of the nutrient broth provided consistently higher titers of virus and the use of the top agar in smaller increments prevented premature solidification. This study then compared the standard ASTM F1671 (using bacteriophage ϕχ174) with a modified dot-blot method to assess viral penetration of PPE materials. The results indicated that ASTM F1671 and the dot-blot apparatus methods were equivalent. The dot-blot method described here is less labor intensive and faster than the ASTM F1671 method. However, using the dot-blot system, which uses antibodies to detect the bacteriophage and signal amplification, does not indicate if virus viability or infectivity is retained, whereas the ASTM F1671 method indicates both. Nonetheless, the method presented in this investigation is a substantial improvement of a standard method for viral challenge testing of PPE materials.

Posthospital home visit as teaching tool for internal medicine residents.

Internal medicine residency programs consider effectively discharging patients from the hospital an important training milestone. However, it is rare for residents to have the opportunity to follow discharged patients into the community and see discharge plans in action. This curriculum provided residents with the opportunity to evaluate patients in their homes after they were discharged from the hospital to assess the alignment of the discharge plan with patients' real-life circumstances. Thirty-nine internal medicine residents participated in a structured exercise during a posthospital discharge home visit to older patients they cared for during the hospital admission. After completing the exercise, residents were asked what they learned from the experience. We found that by visiting patients' homes, residents were able to better assess patient needs, which highlighted the necessity for more individualized discharge plans with regard to in-home functioning, communication with caregivers, and medication reconciliation. Further, the posthospital visit exercise enhanced residents' awareness of challenges in developing and implementing discharge care plans for complex older patients.

Properties of Electropolymerized Dopamine and Its Analogues.

This work reports a study of electropolymerization kinetics, film thickness, stability, and antifouling properties of polydopamine (PDA) and its three analogues: poly(3-(3,4-dihydroxyphenyl)-l-alanine) (PL-DOPA), poly(5-hydroxytryptophan) (PL-5-HTP), and poly(Adrenalin) (PAdrenalin). It was observed that the number of the hydroxyl groups on the benzene ring and the type (primary vs secondary) of amine group significantly affect the electropolymerization kinetics and thus the thickness of the obtained polymer films. Monomers with two hydroxyl groups (except Adrenalin) resulted in films that were thicker (∼10-15 nm) than the one with only one hydroxyl group (PL-5-HTP) (∼5-8 nm) under similar conditions. Adrenalin containing a secondary amino group could not be deposited onto the ITO substrate, while the other three compounds containing a primary amino group completely covered the ITO. The PDA films had better electrochemical stability than the other films. No film showed stable antifouling surfaces against protein.

Cumulative Disaster Exposure and Mental and Physical Health Symptoms Among a Large Sample of Gulf Coast Residents.

A large body of research has linked disaster exposure to adverse mental and physical health outcomes. Few studies, however, have explored the cumulative impact of exposure to multiple disasters. Participants (N = 8,366) from the National Institute of Environmental Health Sciences Gulf Long-Term Follow-Up Study were classified as having been exposed to both, either, or neither Hurricane Katrina and the Deepwater Horizon oil spill (DHOS). Participants also reported on a range of mental and physical health symptoms. Logistic regression models found that participants who were exposed to both disasters had significantly higher odds of probable generalized anxiety disorder, odds ratio (OR) = 1.72, 95% CI [1.52, 1.96]; major depression, OR = 1.53, 95% CI [1.32, 1.77]; and posttraumatic stress disorder, OR = 2.51, 95% CI [2.03, 3.10], than participants who were exposed to only one disaster, ps < .001. Additionally, a linear regression model found that participants who were exposed to both disasters had significantly more physical health symptoms at the time of the spill than those who were exposed to only one disaster, B = 0.99, SE = .20, p < .001. The results indicate that cumulative disaster exposure confers enhanced risk for adverse mental and physical health outcomes. The findings demonstrate that screening for prior exposure among disaster-affected individuals might identify those at greatest risk for adverse health outcomes.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Exposición Acumulativa a Desastres y Síntomas de Salud Mentales y Físicos entre una Amplia Muestra de Residentes del Golfo de México EXPOSICION ACUMULATIVA AL DESASTRE Y SINTOMAS DE SALUD Un vasta serie de investigaciones ha vinculado la exposición a desastres con resultados adversos en la salud mental y física. Sin embargo, escasos estudios han explorado el impacto acumulativo de la exposición a múltiples desastres Los participantes (N = 8,366) del Estudio de Seguimiento a Largo Plazo del Golfo del Instituto Nacional de Ciencias de la Salud Ambiental fueron clasificados como expuesto a ambos, ya sea al Huracán Katrina o al derrame de petróleo de Deepwater Horizon (DHOS en sus siglas en inglés). Los participantes también informaron un rango de síntomas de salud mental y física. Modelos de regresión logística encontraron que los participantes que estuvieron expuestos a ambos desastres tuvieron probabilidades significativamente más altas de presentar trastorno de ansiedad generalizada, proporción de probabilidades (OR) = 1.72, IC 95% [1.52, 1.96]; depresión mayor, OR = 1,53, IC del 95% [1,32, 1,77]; y trastorno de estrés postraumático, OR = 2.51, IC 95% [2.03, 3.10], comparado con los participantes que estuvieron expuestos a un sólo desastre, ps<.001. Adicionalmente, un modelo de regresión lineal encontró que los participantes que fueron expuestos a ambos desastres tuvieron significativamente más síntomas de salud física en el momento del derrame que aquellos que estuvieron expuestos a un sólo desastre, B = 0.99, SE = .20, p <.001. Los resultados indican que la exposición acumulativa al desastre confiere mayor riesgo de resultados adversos para la salud mental y física. Los hallazgos demuestran que la detección de la exposición previa entre individuos afectados por un desastre podría identificar aquellos con mayor riesgo para presentar resultados adversos para la salud.