Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.

Medical education from the point of view of medical students: Results from four participatory Delphi panels in Quito, Ecuador.

BACKGROUND: Medical curricula have historically been designed in a top-down approach, usually excluding students. While Delphi panels have been used as a tool for medical education curricula design, none have been conducted in Ecuador. In addition, no such approach has ever included students both as panelists and researchers. MATERIAL AND METHODS: Four Delphi panels were developed and conducted using a participatory approach that allowed medical students to take part both as expert panelists and researchers: specifically, students developed the questionnaire and conducted a qualitative synthesis. Questionnaire responses were anonymized and dispatched online to panelists. The information was organized and collected to develop the qualitative syntheses and prepare the final statements. RESULTS: Thirty-two medical students participated between February and May 2018. A total of 32 questions were developed, corresponding to five different categories. For some questions, consensus was reached; for other questions, general statements were obtained.Discussion and conclusion: Developing the questionnaire, responding to it and analyzing the answers allowed students to raise significant concerns regarding medical education topics proposing relevant policy and curricula change. Participatory Delphi panels can be an efficient tool to obtain organized feedback, improve student class involvement, and promote research skills.

Altitude effects on technology and productivity of small bovine farms (milk meat) in Veracruz (Gulf of Mexico).

The dual-purpose bovine system represents 98.4% of the bovine livestock of Veracruz, the main cattle-producing state of Mexico. This system supplies calves to meat companies, a sector in which Veracruz has been the national leader in the last decade. The objective of the present study was to analyze the effect of the altitudinal zonation of farms on livestock technology and productivity in a microbasin of the Gulf of Mexico where small farms predominate. Structured interviews were applied to producers located in three altitudinal zones (at average altitudes of 50, 140, and 450 m, respectively, for lower, middle, and upper zones). Sample size was 135 farms having similar land surface (within a range of 15-22 ha). The results indicated multiple differences among farms located in the three zones. Farms in the middle and lower zones presented higher productive indicators than those in the upper zone. Differences in herd structure and management resulted in important differences in productivity, income, and profits in milk and calf production. We concluded from this study that altitudinal zonation in Veracruz had a clear effect on the differentiation of small farms, which are representative of dual-purpose cattle. The upper zone performs cattle activity under conditions with greater disadvantages in the analyzed region.

Reductions of plant cover induced by sheep grazing change the above-belowground partition and chemistry of organic C stocks in arid rangelands of Patagonian Monte, Argentina.

The objective of this study was to estimate the size and chemical quality of the total organic C stock and its partition between above-belowground plant parts and soil at sites with different plant cover induced by sheep grazing in the arid Patagonian Monte. This study was conducted at six representative sites with increasing signs of canopy disturbance attributed to grazing pressure. We used faeces density as a proxy of grazing pressure at each site. We assessed the total plant cover, shrub and perennial grass cover, total standing aboveground biomass (AGB), litter mass and belowground biomass (BGB) at each site. We further estimated the content of organic C, lignin and soluble phenols in plant compartments and the content of organic C, organic C in humic substances (recalcitrant C) and water soluble C (labile C) in soil at each site. Total plant cover was significantly related to grazing pressure. Standing AGB and litter mass decreased with increasing canopy disturbance while BGB did not vary across sites. Total organic C stock and the organic C stock in standing AGB increased with increasing total plant, shrub, and perennial grass cover. The organic C stock in litter mass increased with increasing total plant and shrub cover, while the organic C stock in BGB did not vary across sites. Lignin content in plant compartments increased with increasing total and shrub cover, while soluble phenols content did not change across sites. The organic C stock and the water soluble C content in soil were positively associated with perennial grass cover. Changes in total plant cover induced by grazing pressure negatively affected the size of the total organic C stock, having minor impact on the size of belowground than aboveground components. The reduction of perennial grass cover was reflected in decreasing chemical quality of the organic C stock in soil. Accordingly, plant managerial strategies should not only be focused on the amount of organic C sequestered but also on the chemical quality of organic C stocks since C chemistry could have an important impact on ecosystem functioning.

Meaningful traits for grouping plant species across arid ecosystems.

Grouping species may provide some degree of simplification to understand the ecological function of plants on key ecosystem processes. We asked whether groups of plant species based on morpho-chemical traits associated with plant persistence and stress/disturbance resistance reflect dominant plant growth forms in arid ecosystems. We selected twelve sites across an aridity gradient in northern Patagonia. At each site, we identified modal size plants of each dominant species and assessed specific leaf area (SLA), plant height, seed mass, N and soluble phenol concentration in green and senesced leaves at each plant. Plant species were grouped according with plant growth forms (perennial grasses, evergreen shrubs and deciduous shrubs) and plant morphological and/or chemical traits using cluster analysis. We calculated mean values of each plant trait for each species group and plant growth form. Plant growth forms significantly differed among them in most of the morpho-chemical traits. Evergreen shrubs were tall plants with the highest seed mass and soluble phenols in leaves, deciduous shrubs were also tall plants with high SLA and the highest N in leaves, and perennial grasses were short plants with high SLA and low concentration of N and soluble phenols in leaves. Grouping species by the combination of morpho-chemical traits yielded 4 groups in which species from one growth form prevailed. These species groups differed in soluble phenol concentration in senesced leaves and plant height. These traits were highly correlated. We concluded that (1) plant height is a relevant synthetic variable, (2) growth forms adequately summarize ecological strategies of species in arid ecosystems, and (3) the inclusion of plant morphological and chemical traits related to defenses against environmental stresses and herbivory enhanced the potential of species grouping, particularly within shrubby growth forms.

Effects of long-term grazing disturbance on the belowground storage of organic carbon in the Patagonian Monte, Argentina.

The objective of this study was to analyze the effect of grazing disturbance on the amount and the spatial distribution (vertical and horizontal) of root biomass and soil organic carbon (SOC) in order to evaluate whether grazing alters the belowground storage of organic carbon (C) in arid rangelands of the Patagonian Monte. We selected three representative sites (3 ha each) with low, moderate and high grazing disturbance located far, mid-distance and near the watering point, respectively, in rangelands submitted to sheep grazing for more than 100 years. We assessed the canopy structure and identified the four most frequent plant patch types at each site. We selected four replications of each patch type and extracted a soil sample (0-30 cm depth) underneath the canopy and in the middle of the nearest inter-patch bare soil area in winter and summer. We assessed the root and soil dry mass and the respective organic C concentration in each sample and then we estimated the total belowground organic C storage at each site. Total plant and perennial grass cover were lower with high than low grazing disturbance while the reverse occurred with dwarf shrub cover. High grazing disturbance led to the increase in total root biomass in the whole soil profile of patch areas and in the upper soil of inter-patch areas. SOC was higher in patch than in inter-patch areas at all sites but at both areas was reduced with high grazing disturbance. This was probably the result of the low total plant cover and the low and recalcitrant contribution of above and below-ground plant litter to soils at sites with high grazing disturbance. Accordingly, these changes did not result in variations in the total belowground organic C storage. We concluded that high grazing disturbance did not affect the total belowground organic C storage but led to changes in the spatial patterning of this organic C storage (i.e shifting from soil to roots).

A potential therapeutic strategy based on acute oxidative stress induction for wild-type NRF2/KEAP1 lung squamous cell carcinoma.

Extensive efforts have been conducted in the search for new targetable drivers of lung squamous cell carcinoma (LUSC); to date, however, candidates remain mostly unsuccessful. One of the oncogenic pathways frequently found to be active in LUSC is NFE2L2 (NRF2 transcription factor), the levels of which are regulated by KEAP1. Mutations in NFE2L2 or KEAP1 trigger NRF2 activation, an essential protector against reactive oxygen species (ROS). We hypothesized that the frequency of NRF2 activation in LUSC (∼35 %) may reflect a sensitivity of LUSC to ROS. Results from this study reveal that whereas tumors containing active forms of NRF2 were protected, ROS induction in wild-type NFE2L2/KEAP1 LUSC cells triggered ferroptosis. The mechanism of ROS action in normal-NRF2 LUSC cells involved transient NRF2 activation, miR-126-3p/miR-126-5p upregulation, and reduction of p85ß and SETD5 levels. SETD5 levels reduction triggered pentose pathway gene levels increase to toxic values. Simultaneous depletion of p85ßPI3K and SETD5 triggered LUSC cell death, while p85ßPI3K and SETD5 overexpression rescued survival of ROS-treated normal-NRF2 LUSC cells. This shows that the cascade involving NRF2 > miR-126-3p, miR-126-5p > p85ßPI3K and SETD5 is responsible for ROS-induced cell death in normal-NRF2 LUSC. Transient ROS-induced cell death is shown in 3D spheroids, patient-derived organoids, and in xenografts of wild-type NFE2L2/KEAP1 LUSC cells, supporting the potential of acute local ROS induction as a therapeutic strategy for LUSC patients with normal-NRF2.

Effectiveness of a specific follow up program for the management of the mental components of post-intensive care syndrome and chronic pain after COVID-19: results from the PAIN-COVID randomized clinical trial.

BACKGROUND: Critical COVID-19 survivors are at risk of developing Post-intensive Care Syndrome (PICS) and Chronic ICU-Related Pain (CIRP). We determined whether a specific care program improves the quality of life (QoL) of patients at risk of developing PICS and CIRP after COVID-19. METHODS: The PAIN-COVID trial was a parallel-group, single-centre, single-blinded, randomized controlled trial. The intervention consisted of a follow up program, patient education on PICS and pain, and a psychological intervention based on Rehm's self-control model in patients with abnormal depression scores (≥8) in the Hospital Anxiety and Depression Scale (HADS) at the baseline visit. QoL was evaluated with the 5-level EQ 5D (EQ 5D 5 L), mood disorders with the HADS, post-traumatic stress disorder (PTSD) with the PCL-5 checklist, and pain with the Brief Pain Inventory short form, the Douleur Neuropathique 4 questionnaire, and the Pain Catastrophizing Scale. The primary outcome was to determine if the program was superior to standard-of-care on the EQ visual analogue scale (VAS) at 6 months after the baseline visit. The secondary outcomes were EQ VAS at 3 months, and EQ index, CIRP incidence and characteristics, and anxiety, depression, and PTSD at 3 and 6 months after baseline visits. CONCLUSIONS: This program was not superior to standard care in improving QoL in critical COVID-19 survivors as measured by the EQ VAS. However, our data can help establish better strategies for the study and management of PICS and CIRP in this population. TRIAL REGISTRATION: # NCT04394169, registered on 5/19/2020.

Negative screening colonoscopy after a positive guaiac faecal occult blood test: not a contraindication to continued screening.

AIM: In guaiac faecal occult blood test (gFOBT) screening at least 50% of positive individuals will have a colonoscopy negative for colorectal neoplasia. The question of continuing screening in this group has not been addressed. METHOD: Data on participants aged 50-69 years with a positive gFOBT result and a negative colonoscopy were followed through the biennial screening pilot conducted between 2000 and 2007 in Scotland. RESULTS: In the first screening round, 1527 colonoscopies were negative for neoplasia. 1300 were re-invited in the second round, 905 accepted, and 157 had a positive gFOBT result, giving a positivity rate of 17.4%. Colonoscopy revealed 20 subjects with adenoma and six with invasive cancer. In the third screening round 1031 were invited for a third time and 730 accepted: 55 had a positive gFOBT test, giving a positivity rate of 7.5%. In this group, six colonoscopies revealed adenomas but there were no cancers diagnosed. In the third screening round, 108 individuals had had two positive gFOBT results and two subsequent negative colonoscopies. Eighty-four were invited for a third gFOBT, 66 accepted and 19 (25.6%) had a positive result none of whom had an adenoma or carcinoma. CONCLUSION: These data indicate that a negative colonoscopy following a positive gFOBT is not a contraindication for further screening, although this is likely to have a low yield of neoplastic pathology after two negative colonoscopies.

Role of the PI3K regulatory subunit in the control of actin organization and cell migration.

Cell migration represents an important cellular response that utilizes cytoskeletal reorganization as its driving force. Here, we describe a new signaling cascade linking PDGF receptor stimulation to actin rearrangements and cell migration. We demonstrate that PDGF activates Cdc42 and its downstream effector N-WASP to mediate filopodia formation, actin stress fiber disassembly, and a reduction in focal adhesion complexes. Induction of the Cdc42 pathway is independent of phosphoinositide 3-kinase (PI3K) enzymatic activity, but it is dependent on the p85alpha regulatory subunit of PI3K. Finally, data are provided showing that activation of this pathway is required for PDGF-induced cell migration on collagen. These observations show the essential role of the PI3K regulatory subunit p85alpha in controlling PDGF receptor-induced cytoskeletal changes and cell migration, illustrating a novel signaling pathway that links receptor stimulation at the cell membrane with actin dynamics.