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1.
Emergencias (Sant Vicenç dels Horts) ; 32(2): 111-117, abr. 2020. ilus, tab
Artigo em Espanhol | IBECS-Express | ID: ibc-ET2-4591

RESUMO

Objetivo: La simulación interprofesional (SIP) es eficaz para aprender gestión de recursos de crisis. La modalidad de debriefing utilizada en la SIP puede influir en el rendimiento de los participantes y en su integridad psicológica. Se evalúa y compara el rendimiento de un debriefing estándar (DE) –colectivo– con un debriefing combinado (DC) –individual y colectivo– en cursos de SIP en escenarios que simulan pacientes con patología aguda y grave. Método: Ensayo controlado, aleatorizado y multicéntrico. Se aleatorizó el tipo de debriefing realizado (DE o DC) en las sesiones de SIP. El rendimiento del debriefing se evaluó con la escala TEAM (Team Emergency Assessment Measure). La calidad de la SIP fue valorada por los participantes con la escala DASH (Debriefing Assessment for Simulation in Healthcare©). Resultados. Se aleatorizaron 40 cursos de SIP de los que se analizaron 30. Quince realizaron DE y 15 DC. Ambos grupos mejoraron entre la pre y la posprueba (p < 0,01), pero no hubo diferencias en el rendimiento global entre ambas modalidades de debriefing (p = 0,64). El DC obtuvo mejores resultados que el DE en la capacidad de liderazgo (p < 0,05), en la percepción de seguridad psicológica y en la experiencia de aprendizaje eficaz (p < 0,05). Conclusiones: Durante la SIP en situaciones de crisis, el debriefing mejora el rendimiento de los participantes, sin diferencias entre un DE y un DC. El DC podría ser más efectivo para mejorar la capacidad de liderazgo, la seguridad psicológica y la experiencia del aprendizaje


Objective: Interprofessional simulation (IPS) training is an effective way to learn crisis resource management. The type of debriefing used in IPS training may affect participants' performance and their level of psychological safety. We aimed to assess and compare performance after standard collective debriefing versus a combination of individual and collective debriefing ("combined" approach). Methods: Randomized, controlled multicenter trial. IPS sessions were randomized to have either standard or combined debriefing. Each team's performance in the IPS session was assessed with the Team Emergency Assessment Measure. The participants assessed the debriefing quality with the Debriefing Assessment for Simulation in Healthcare. Results: Forty IPS sessions were randomized, and 30 were analyzed, 15 using standard collective debriefing and 15 the combined individual–collective method. Teams' performance improved with both types of debriefing, based on pre-post testing (P<.01), and there were no significant differences in overall performance scores between the 2 types of debriefing (P=.64). However, the combined approach was associated with higher scores for leadership skills (P<.05) and psychological safety, and the participants' learning experience was better (P<.05). Conclusions: During IPS courses on crisis resource management, debriefing improves participants' performance, but similar overall results can be obtained with both debriefing methods. Combined debriefing might be more effective for improving participants' leadership skills and psychological safety and also provide a better learning experience

2.
NMR Biomed ; : e4269, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32133713

RESUMO

Hyperpolarized (HP) 13 C MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since 13 C -lactate signal levels obtained from HP 13 C imaging depend on multiple factors, such as the rate of 13 C substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP 13 C metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived from an MDA-MB-231 xenograft model in nude rats were used to test for correlations between the in vivo 13 C data and the ex vivo measures. The lactate-to-pyruvate ratio from HP 13 C MRI was strongly correlated with [1- 13 C ]lactate concentration measured from the extracts using NMR (R = 0.69, p < 0.05), as well as negatively correlated with tumour wet weight (R = - 0.60, p < 0.05). In this tumour model, both MCT1 and MCT4 expressions were positively correlated with wet weight ( ρ = 0.78 and 0.93, respectively, p < 0.01). Lactate pool size and the lactate-to-pyruvate ratio were not significantly correlated.

3.
Neurogastroenterol Motil ; : e13839, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167628

RESUMO

BACKGROUND: Opioid use has reached epidemic proportions. In contrast to the known effect of opioids on gut transit, the effect on rectal sensorimotor function has not been comprehensively investigated. METHODS: Cross-sectional (hypothesis-generating) study of anorectal physiology studies in 2754 adult patients referred to a tertiary unit (2004-2016) for investigation of functional constipation (defined by "derived" Rome IV core criteria). Statistical associations between opioid usage, symptoms, and anorectal physiological variables were investigated. Opioids were sub-classified as prescriptions for mild-moderate or moderate-severe pain. KEY RESULTS: A total of 2354 patients (85.5%) were classified as non-opioid users, 162 (5.9%) as opioid users for mild-moderate pain, and 238 (8.6%) for moderate-severe pain. Opioids for moderate-severe pain were associated with increased symptomatic severity (Cleveland Clinic constipation score 18.5 vs 15.1; mean difference 2.9 [95%-CI 2.3-3.6]; P < .001), rectal hyposensitivity (odds ratio 1.74 [95%-CI 1.23-2.46]; P = .002), functional evacuation disorders (odds ratio 1.73 [95%-CI 1.28-2.34]; P < .001), and delayed whole-gut transit (odds ratio 1.68 [95%-CI 1.19-2.37]; P = .003). Differences in anorectal variables between opioid users for mild-moderate pain and non-opioid users were not statistically significant. Hierarchical opioid use (non vs mild-moderate vs moderate-severe) was associated with decreasing proportions of patients with no physiological abnormality on testing (40.2% vs 38.1% vs 29.2%) and increasing proportions with both delayed whole-gut transit and rectal sensorimotor dysfunction (16.6% vs 17.5% vs 28.5%). CONCLUSIONS AND INFERENCES: Opioid use is over-represented in patients referred for investigation of constipation. Opioids for moderate-severe pain are associated with rectal sensorimotor abnormalities. Further studies are required to determine whether this association indicates causation.

5.
Neuromodulation ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32153080

RESUMO

BACKGROUND: In sacral neuromodulation (SNM), stimulation programming plays a key role to achieve success of the therapy. However to date, little attention has been given to the best ways to set and optimize SNM programming during the test and chronic stimulation phases of the procedure. OBJECTIVE: Standardize and make SNM programming easier and more efficient for the several conditions for which SNM is proposed. METHODS: Systematic literature review and collective clinical experience report. RESULTS: The basic principles of SNM programming are described. It covers choice of electrode configuration, stimulation amplitude, pulse frequency and pulse widths, while use of cycling is also briefly discussed. Step-by-step practical flow charts developed by a group of 13 European experts are presented. CONCLUSIONS: Programming of SNM therapy is not complex. There are few programming settings that seem beneficial or significantly impact patient outcomes. Only four basic electrode configurations could be identified according to four different options to define the cathode. In a majority of patients, the proposed stimulation parameters will allow a satisfactory improvement for long periods of time. A regular follow-up is, however, necessary to assess and eventually optimize results, as well as to reassure patients.

6.
Sci Rep ; 10(1): 3796, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123245

RESUMO

Sea-level rise (SLR) induced flooding is often envisioned as solely originating from a direct marine source. This results in alternate sources such as groundwater inundation and storm-drain backflow being overlooked in studies that inform planning. Here a method is developed that identifies flooding extents and infrastructure vulnerabilities that are likely to result from alternate flood sources over coming decades. The method includes simulation of flood scenarios consisting of high-resolution raster datasets featuring flood-water depth generated by three mechanisms: (1) direct marine flooding, (2) storm-drain backflow, and (3) groundwater inundation. We apply the method to Honolulu's primary urban center based on its high density of vulnerable assets and present-day tidal flooding issues. Annual exceedance frequencies of simulated flood thresholds are established using a statistical model that considers predicted tide and projections of SLR. Through assessment of multi-mechanism flooding, we find that approaching decades will likely feature large and increasing percentages of flooded area impacted simultaneously by the three flood mechanisms, in which groundwater inundation and direct marine flooding represent the most and least substantial single-mechanism flood source, respectively. These results illustrate the need to reevaluate main sources of SLR induced flooding to promote the development of effective flood management strategies.

7.
Cancer Med ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32130793

RESUMO

BACKGROUND: The goal of surveillance testing is to enable curative salvage therapy through early disease detection, however supporting evidence in gastroesophageal adenocarcinoma is limited. We evaluated frequency of successful salvage therapy and outcomes in patients who underwent surveillance. METHODS: A single-site, retrospective cohort study was conducted to identify all patients who received curative resection for gastroesophageal adenocarcinoma. Surveillance testing were those investigations not triggered by abnormal symptoms, physical examination, or blood tests. Successful salvage therapy was any potentially curative therapy for disease recurrence which resulted in postrecurrence disease-free survival ≥2 years. Time-to-event data were analyzed using the Kaplan-Meier method and log rank tests. RESULTS: Between 2011 and 2016, 210 consecutive patients were reviewed. Esophageal (14%), gastroesophageal junction (40%), and gastric adenocarcinomas (45%) were treated with surgery alone (29%) or multimodality therapy (71%). Adjuvant therapy was administered in 35%. At median follow-up of 38.3 months, 5-year overall survival (OS) rate was 56%. Among 97 recurrences, 53% were surveillance-detected, and 46% were symptomatic. None was detected by surveillance endoscopy. Median time-to-recurrence (TTR) was 14.8 months. Recurrences included locoregional only (4%), distant (86%), and both (10%). Salvage therapy was attempted in 15 patients, 4 were successful. Compared to symptomatic recurrences, patients with surveillance-detected recurrences had longer median OS (36.2 vs 23.7 months, P = .004) and postrecurrence survival (PRS, 16.5 vs 4.6 months, P < .001), but similar TTR (16.2 vs 13.3 months, P = .40) and duration of palliative chemotherapy (3.9 vs 3.3 months, P = .64). CONCLUSIONS: Among patients surveyed, 96% of recurrences were distant, and salvage therapy was successful in only 1.9% of patients. Longer OS in patients with surveillance-detected compared to symptomatic recurrences was not associated with significant earlier disease detection, and may be contributed by differences in disease biology. Further prospective data are warranted to establish the benefit of surveillance testing in gastroesophageal adenocarcinoma.

8.
9.
Artigo em Inglês | MEDLINE | ID: mdl-32222079

RESUMO

BACKGROUND: Children reared in institutions experience profound deprivation that is linked to impairments in social communication (SC). However, little is known about the long-term consequences of institutional rearing on SC through adolescence, and how SC deficits relate to broad-spectrum psychopathology. It is also unclear whether early removal from deprivation and placement into socially enriched environments remediates these difficulties. METHODS: Children reared in Romanian institutions from the Bucharest Early Intervention Project were randomly assigned to care as usual or foster care intervention in early childhood. An age- and sex-matched group of never-institutionalized children was also recruited. SC data from 208 children at age 8 and 129 children at 16 were collected using the Social Communication Questionnaire. Psychopathology was assessed as saved factor scores for general (P) and specific internalizing (INT) and externalizing (EXT) problems. We examined (a) whether institutional rearing is associated with continued SC deficits into adolescence; (b) whether early placement into foster care mitigates risk for SC problems; and (c) associations between SC and psychopathology from middle childhood (age 8) to adolescence (age 16). RESULTS: Findings suggest that: (a) institutionally-reared children have significantly more SC problems than never-institutionalized children at age 16; (b) children placed into foster care early in life have fewer problems with reciprocal social interaction compared to those with prolonged institutional rearing; and (c) deficits in SC at age 8 partially account for the link between institutional rearing and general psychopathology at age 16. CONCLUSIONS: Early deprivation is associated with impairments in SC that persist into adolescence, with evidence for the remedial benefit of family-based care in the domain of reciprocal social interaction. Moreover, deficits in SC among ever-institutionalized children in middle childhood may increase the risk of broad-spectrum psychopathology in adolescence, thus providing one putative target for early intervention to safeguard against later psychiatric problems.

10.
Clin Geriatr Med ; 36(2): 265-279, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32222301

RESUMO

Electroconvulsive therapy (ECT) remains an important treatment of geriatric patients. ECT treats severe depression, mania, psychosis, catatonia, and comorbid depression and agitation in dementia. ECT also serves a crucial role in treating urgent illness requiring expedient recovery, such as catatonia, or in patients with severe suicidal ideation or intent. ECT is even more effective in the elderly than in mixed-age adult populations. ECT is a safe treatment option with few medical contraindications. Cognitive effects are largely transient, even in patients with preexisting cognitive impairment.

11.
ACS Nano ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32186852

RESUMO

Chiral surfaces are of growing interest for enantioselective adsorption and reactions. While metal surfaces can be prepared with a wide range of chiral surface orientations, chiral oxide surface preparation is more challenging. We demonstrate the chirality of a metal surface can be used to direct the homochiral growth of a thin film chiral oxide. Specifically, we study the chiral "29" copper oxide, formed by oxidizing a Cu(111) single crystal at 650 K. Surface structure spread single crystals, which expose a continuous distribution of surface orientations as a function of position on the crystal, enable us to systematically investigate the mechanism of chirality transfer between the metal and the surface oxide with high-resolution scanning tunneling microscopy. We discover that the local underlying metal facet directs the orientation and chirality of the oxide overlayer. Importantly, single homochiral domains of the "29" oxide were found in areas where the Cu step edges that templated growth were ≤20 nm apart. We use this information to select a Cu(239 241 246) oriented single crystal and demonstrate that a "29" oxide surface can be grown in homochiral domains by templating from the subtle chirality of the underlying metal crystal. This work demonstrates how a small degree of chirality induced by slight misorientation of a metal surface (∼1 sites/20 nm2) can be amplified by oxidation to yield a homochiral oxide with a regular array of chiral oxide pores (∼75 sites/20 nm2). This offers a general approach for making chiral oxide surfaces via oxidation of an appropriately "miscut" metal surface.

12.
Am J Sports Med ; : 363546520906158, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32182091

RESUMO

BACKGROUND: Femoral tunnels that are not anatomically placed within the native anterior cruciate ligament (ACL) footprint during ACL reconstruction are associated with residual instability, graft rupture, and poor clinical outcomes. Although surgeons may intend to place their femoral tunnels within the native ACL attachment, this is not always achieved. This study assesses the variation between intended and achieved femoral tunnel positions in a large cohort of experienced ACL surgeons. HYPOTHESIS: The accuracy with which experienced ACL surgeons achieve their intended femoral tunnel position is dependent on viewing portal, localization strategy, and drilling technique. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 221 surgeons indicated their intended femoral tunnel location on a true lateral radiograph of a cadaveric knee specimen and a scaled photograph. Each surgeon then arthroscopically demonstrated the femoral tunnel on the specimen. The position was captured using fluoroscopy. The Euclidean distance (the straight-line distance between 2 points) between the intended and achieved tunnel positions, referenced to a grid applied to the lateral femoral condyle, was compared. Data were analyzed according to surgeons' viewing portal (anteromedial [AM] or anterolateral [AL]), tunnel localization strategy (offset aimer, estimation from landmarks, ACL ruler, or C-arm fluoroscopy), and stated drilling technique (transtibial, AM portal, or outside-in). RESULTS: Surgeons who viewed the lateral intercondylar notch wall through the AM portal were closer (mean distance, 9.5) to their intended position than those who viewed through the AL portal (mean distance, 15.1; P < .0001). By localization strategy, the mean distance between achieved and intended tunnel positions was greater for surgeons who used an offset aimer (14.5) and estimated the femoral tunnel position (12.9) than for those using a malleable ACL ruler (8.1; P < .0001) and fluoroscopy (4.3; P < .0001). Surgeons' preferred drilling technique (AM portal, transtibial, or outside-in) had no effect on distance between intended and achieved positions. However, the mean achieved position was higher in the intercondylar notch for those using transtibial drilling (P < .042). CONCLUSION: Surgeons using the AM portal to view the femoral attachment site were closer to their intended tunnel position than those who viewed it with the arthroscope in the AL portal. Surgeons who used fluoroscopy to localize femoral tunnel position were the closest to their intended position. Those who used estimation or an offset aimer had the farthest distance between achieved and intended tunnel positions. CLINICAL RELEVANCE: Although accurate tunnel placement can be achieved using any method, given the disparity between intended and achieved tunnel positions, it may be advisable, even for high-volume surgeons, to verify the placement of their tunnels using either fluoroscopy or a malleable ACL ruler to ensure that they achieve their intended position. Fluoroscopy may be particularly useful for cases where the native femoral stump is no longer visible and for revisions. Viewing through the AM portal is recommended to aid accuracy of tunnel placement.

14.
Cancer Immunol Res ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209637

RESUMO

Resistance to cytotoxic T cells is frequently mediated by loss of MHC class I expression or IFNγ signaling in tumor cells, such as mutations of B2M or JAK1 genes. NK cells could potentially target such resistant tumors, but suitable NK cell-based strategies remain to be developed. We hypothesized that such tumors could be targeted by NK cells if sufficient activating signals were provided. Human tumors frequently express the MICA and MICB ligands of the activating NKG2D receptor, but proteolytic shedding of MICA/B represents an important immune evasion mechanism in many human cancers. We showed that B2M- and JAK1-deficient metastases were targeted by NK cells following treatment with a monoclonal antibody (mAb) that blocks MICA/B shedding. We also demonstrated that the FDA-approved HDAC inhibitor panobinostat and a MICA/B antibody acted synergistically to enhance MICA/B surface expression on tumor cells. The HDAC inhibitor enhanced MICA/B gene expression, whereas the MICA/B antibody stabilized the synthesized protein on the cell surface. The combination of panobinostat and the MICA/B antibody reduced the number of pulmonary metastases formed by a human melanoma cell line in NSG mice reconstituted with human NK cells. NK cell-mediated immunity induced by a mAb specific for MICA/B, therefore, provides an opportunity to target tumors with mutations that render them resistant to cytotoxic T cells.

15.
PLoS Pathog ; 16(3): e1008298, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32134991

RESUMO

Although acute melioidosis is the most common outcome of Burkholderia pseudomallei infection, we have documented a case, P314, where disease severity lessened with time, and the pathogen evolved towards a commensal relationship with the host. In the current study, we used whole-genome sequencing to monitor this long-term symbiotic relationship to better understand B. pseudomallei persistence in P314's sputum despite intensive initial therapeutic regimens. We collected and sequenced 118 B. pseudomallei isolates from P314's airways over a >16-year period, and also sampled the patient's home environment, recovering six closely related B. pseudomallei isolates from the household water system. Using comparative genomics, we identified 126 SNPs in the core genome of the 124 isolates or 162 SNPs/indels when the accessory genome was included. The core SNPs were used to construct a phylogenetic tree, which demonstrated a close relationship between environmental and clinical isolates and detailed within-host evolutionary patterns. The phylogeny had little homoplasy, consistent with a strictly clonal mode of genetic inheritance. Repeated sampling revealed evidence of genetic diversification, but frequent extinctions left only one successful lineage through the first four years and two lineages after that. Overall, the evolution of this population is nonadaptive and best explained by genetic drift. However, some genetic and phenotypic changes are consistent with in situ adaptation. Using a mouse model, P314 isolates caused greatly reduced morbidity and mortality compared to the environmental isolates. Additionally, potentially adaptive phenotypes emerged and included differences in the O-antigen, capsular polysaccharide, motility, and colony morphology. The >13-year co-existence of two long-lived lineages presents interesting hypotheses that can be tested in future studies to provide additional insights into selective pressures, niche differentiation, and microbial adaptation. This unusual melioidosis case presents a rare example of the evolutionary progression towards commensalism by a highly virulent pathogen within a single human host.

16.
Insects ; 11(3)2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32110919

RESUMO

The olive psyllid, Euphyllura olivina, is a newly invasive species to California with the potential to become an economical pest if it reaches the olive production regions of California's Central Valley. Here, we report on surveys undertaken in California to assess the psyllid's current distribution and the occurrence of parasitism. Additionally, we present results of foreign collections of its parasitoids and initial non-target studies of a possible biological control agent, the Mediterranean parasitoid Psyllaephagus euphyllurae. The current distribution of the psyllid appears to be limited to the California coast between Monterey and San Diego; there have been no reports of infestations on olives in the major production areas of central and northern California. Psyllaephagus euphyllurae was the major primary parasitoid found in our foreign collections. The potential non-target impact of P. euphyllurae was tested on three native North American psyllid species: Neophyllura arctostaphyli, Euglyptoneura nr. robusta, and Calophya nigrella. No P. euphyllurae developed on the non-target species during no-choice tests. Behavioral observations in choice tests confirmed no attack on the non-target hosts, although the parasitoid did remain longer on N. arctostaphyli-infested manzanita plants, and revealed no host feeding behavior.

17.
South Med J ; 113(3): 140-145, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32123930

RESUMO

OBJECTIVES: To explore temporal trends and geographic variations in mortality from prescription opioids from 1999 to 2016. METHODS: Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death files were used to calculate age-adjusted rates and 95% confidence intervals (CIs) and create spatial cluster maps. RESULTS: From 1999 to 2016, counties in West Virginia experienced the highest overall mortality rates in the United States from prescription opioids. Specifically, from 1999 to 2004, the highest rate in West Virginia of 24.87/100,000 (95% CI 17.84-33.73) was the fourth highest in the United States. From 2005 to 2009, West Virginia experienced the highest rate in the United States, 60.72/100,000 (95% CI 47.33-76.71). From 2010 to 2016, West Virginia also experienced the highest rate in the United States, which was 90.24/100,000 (95% CI 73.11-107.36). As such, overall, West Virginia experienced the highest rates in the United States and the largest increases overall of ~3.6-fold between 1999 and 2004 and 2010 and 2016. From 1999 to 2004, Florida had no "hot spots," but from 2006 to 2010 they did appear, and from 2011 to 2016, they disappeared. CONCLUSIONS: These data show markedly divergent temporal trends and geographic variations in mortality rates from prescription opioids, especially in the southern United States. Specifically, although initial rates were high and continued to increase alarmingly in West Virginia, they increased but then decreased in Florida. These descriptive data generate hypotheses requiring testing in analytic epidemiological studies. Understanding the divergent patterns of prescription opioid-related deaths, especially in West Virginia and Florida, may have important clinical and policy implications.

18.
Emergencias ; 32(2): 111-117, 2020.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-32125110

RESUMO

OBJECTIVES: Interprofessional simulation (IPS) training is an effective way to learn crisis resource management. The type of debriefing used in IPS training may affect participants' performance and their level of psychological safety. We aimed to assess and compare performance after standard collective debriefing versus a combination of individual and collective debriefing ("combined" approach). MATERIAL AND METHODS: Randomized, controlled multicenter trial. IPS sessions were randomized to have either standard or combined debriefing. Each team's performance in the IPS session was assessed with the Team Emergency Assessment Measure. The participants assessed the debriefing quality with the Debriefing Assessment for Simulation in Healthcare. RESULTS: Forty IPS sessions were randomized, and 30 were analyzed, 15 using standard collective debriefing and 15 the combined individual-collective method. Teams' performance improved with both types of debriefing, based on pre-post testing (P<.01), and there were no significant differences in overall performance scores between the 2 types of debriefing (P=.64). However, the combined approach was associated with higher scores for leadership skills (P<.05) and psychological safety, and the participants' learning experience was better (P<.05). CONCLUSION: During IPS courses on crisis resource management, debriefing improves participants' performance, but similar overall results can be obtained with both debriefing methods. Combined debriefing might be more effective for improving participants' leadership skills and psychological safety and also provide a better learning experience.

19.
Am J Transplant ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031745

RESUMO

Hypoxia is a major cause of considerable islet loss during the early posttransplant period. Here, we investigate whether shielding islets with human amniotic epithelial cells (hAECs), which possess anti-inflammatory and regenerative properties, improves islet engraftment and survival. Shielded islets were generated on agarose microwells by mixing rat islets (RIs) or human islets (HI) and hAECs (100 hAECs/IEQ). Islet secretory function and viability were assessed after culture in hypoxia (1% O2 ) or normoxia (21% O2 ) in vitro. In vivo function was evaluated after transplant under the kidney capsule of diabetic immunodeficient mice. Graft morphology and vascularization were evaluated by immunohistochemistry. Both shielded RIs and HIs show higher viability and increased glucose-stimulated insulin secretion after exposure to hypoxia in vitro compared with control islets. Transplant of shielded islets results in considerably earlier normoglycemia and vascularization, an enhanced glucose tolerance, and a higher ß cell mass. Our results show that hAECs have a clear cytoprotective effect against hypoxic damages in vitro. This strategy improves ß cell mass engraftment and islet revascularization, leading to an improved capacity of islets to reverse hyperglycemia, and could be rapidly applicable in the clinical situation seeing that the modification to HIs are minor.

20.
Eur Respir Rev ; 29(155)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32024722

RESUMO

Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is a life-threatening complication of chronic hepatosplenic schistosomiasis. It is suggested to be the leading cause of pulmonary arterial hypertension (PAH) worldwide. However, pathophysiological data on Sch-PAH are scarce. We examined the hypothesis that there are pronounced similarities in pathophysiology, haemodynamics, and survival of Sch-PAH and idiopathic PAH (iPAH).This systematic review and meta-analysis was registered in the PROSPERO database (identifier CRD42018104066). A systematic search and review of the literature was performed according to PRISMA guidelines for studies published between 01 January 1990 and 29 June 2018.For Sch-PAH, 18 studies evaluating pathophysiological mechanisms, eight studies on haemodynamics (n=277), and three studies on survival (n=191) were identified. 16 clinical registries reporting data on haemodynamics and survival including a total of 5792 patients with iPAH were included for comparison. Proinflammatory molecular pathways are involved in both Sch-PAH and iPAH. The transforming growth factor (TGF)-ß signalling pathway is upregulated in Sch-PAH and iPAH. While there was no difference in mean pulmonary artery pressure (54±17 mmHg versus 55±15 mmHg, p=0.29), cardiac output (4.4±1.3 L·min-1 versus 4.1±1.4 L·min-1, p=0.046), and cardiac index (2.6±0.7 L·min-1·m-2 versus 2.3±0.8 L·min-1·m-2, p<0.001) were significantly higher in Sch-PAH compared to iPAH, resulting in a lower pulmonary vascular resistance in Sch-PAH (10±6 Woods units versus 13±7 Woods units, p<0.001). 1- and 3-year survival were significantly better in the Sch-PAH group (p<0.001).Sch-PAH and iPAH share common pathophysiological mechanisms related to inflammation and the TGF-ß signalling pathway. Patients with Sch-PAH show a significantly better haemodynamic profile and survival than patients with iPAH.

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