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Acute circulatory dysfunction in patients with sepsis can evolve rapidly into a progressive stage associated with high mortality. Early recognition and adequate resuscitation could improve outcome. However, since the spectrum of clinical presentation is quite variable, signs of hypoperfusion are frequently unrecognized in patients just admitted to the emergency department (ED). Hyperlactatemia is considered a key parameter to disclose tissue hypoxia but it is not universally available and getting timely results can be challenging in low resource settings. In addition, non-hypoxic sources can be involved in hyperlactatemia, and a misinterpretation could lead to over-resuscitation in an unknown number of cases. Capillary refill time (CRT) is a marker of peripheral perfusion that worsens during circulatory failure. An abnormal CRT in septic shock patients after ICU-based resuscitation has been associated with poor outcome. The aim of this study was to determine the prevalence of abnormal CRT in patients with sepsis-related hyperlactatemia in the early phase after ED admission, and its relationship with outcome. We performed a prospective observational study. Septic patients with hyperlactemia at ED admission subjected to an initial fluid resuscitation (FR) were included. CRT and other parameters were assessed before and after FR. CRT-normal or CRT-abnormal subgroups were defined according to the status of CRT following initial FR, and major outcomes were registered. Ninety-five hyperlactatemic septic patients were included. Thirty-one percent had abnormal CRT at ED arrival. After FR, 87 patients exhibited normal CRT, and 8 an abnormal one. Patients with abnormal CRT had an increased risk of adverse outcomes (88% vs. 20% p<0.001; RR 4.4 [2.7-7.4]), and hospital mortality (63% vs. 9% p<0.001; RR 6.7 [2.9-16]) as compared to those with normal CRT after FR. Specifically, CRT-normal patients required less frequently mechanical ventilation, renal replacement therapy, and ICU admission, and exhibited a lower hospital mortality. Hyperlactatemic sepsis patients with abnormal CRT after initial fluid resuscitation exhibit higher mortality and worse clinical outcomes than patients with normal CRT.

Introduction: The clinical presentation of coronavirus disease 2019 (COVID-19) overlaps with many other common cold and influenza viruses. Identifying patients with a higher probability of infection becomes crucial in settings with limited access to testing. We developed a prediction instrument to assess the likelihood of a positive polymerase chain reaction (PCR) test, based solely on clinical variables that can be determined within the time frame of an emergency department (ED) patient encounter.Methods: We derived and prospectively validated a model to predict SARS-CoV-2 PCR positivity in patients visiting the ED with symptoms consistent with the disease.Results: Our model was based on 617 ED visits. In the derivation cohort, the median age was 36 years, 43% were men, and 9% had a positive result. The median time to testing from the onset of initial symptoms was four days (interquartile range [IQR]: 2-5 days, range 0-23 days), and 91% of all patients were discharged home. The final model based on a multivariable logistic regression included a history of close contact (adjusted odds ratio [AOR] 2.47, 95% confidence interval [CI], 1.29-4.7); fever (AOR 3.63, 95% CI, 1.931-6.85); anosmia or dysgeusia (AOR 9.7, 95% CI, 2.72-34.5); headache (AOR 1.95, 95% CI, 1.06-3.58), myalgia (AOR 2.6, 95% CI, 1.39-4.89); and dry cough (AOR 1.93, 95% CI, 1.02-3.64). The area under the curve (AUC) from the derivation cohort was 0.79 (95% CI, 0.73-0.85) and AUC 0.7 (95% CI, 0.61-0.75) in the validation cohort (N = 379).Conclusion: We developed and validated a clinical tool to predict SARS-CoV-2 PCR positivity in patients presenting to the ED to assist with patient disposition in environments where COVID-19 tests or timely results are not readily available.

In the shift from the balance of nature to the flux of nature paradigm, the concept of resilience has gained great traction in ecology. While it has been suggested that the concept of resilience does not imply a genuine departure from the balance of nature paradigm, I shall argue against this stance. To do so, I first show that the balance of nature paradigm and the related conception of a single-state equilibrium relies on what Eliot Sober has named the “Natural State Model (NSM)”, suggesting that the NSM has instead been dismissed in the flux of nature paradigm. I then focus on resilience as the main explanatory concept of the flux paradigm. After distinguishing between two main different understandings of “resilience”, namely engineering resilience and ecological resilience, I argue that the former is close to the concept of balance or stability and still part of the NSM, while the latter is not. Finally, I claim that ecological resilience is inconsistent with the NSM, concluding that this concept–being incompatible with the NSM–is not part of the balance of nature paradigm but rather a genuinely new explanatory tool.

Approaches that are transdisciplinary and participatory can help to address complex socio-ecological issues by integrating multiple disciplinary perspectives while taking into account the different needs and experiences of community members and other stakeholders. Despite this promise, such approaches are rarely applied within the scientific community, as researchers and public actors often lack the training, practice and reference cases required to handle the working relationships and translations of terminology, ideas and values across multiple bodies of knowledge. A case study described in this manuscript depicts a group of researchers, artists and citizens consciously engaged in the construction of a transdisciplinary process as part of a 40-day ‘citizen science’ experiment focussed on assessing soil fertility in the urban area of Milan, Italy. The group drew from recognised scientific approaches, applied agronomic methodologies, artistic practices and technological tools, integrating them into a hybrid process of collective and participatory inquiry. As a quantitative outcome of the experiment, a dataset of bio-chemical parameters was generated, which was enriched by agronomic interpretations but also by artistic and reflective materials. Importantly, the process developed transdisciplinary and participatory skills, as it created a potentially replicable procedure of engagement, analysis and presentation for use in other citizen science settings. This article presents the context, the multiple objectives of the research and the applied approach and its timeline. Described in detail are the process of designing and conducting the experiment by involving an extended research community—including both junior and senior researchers—in progressive steps. Quantitative and qualitative results are provided. The findings are meant to contribute case material and methods to inform the advancement of transdisciplinary research approaches within the scientific community as well as examples of ways to transcend the boundaries of science to include artists and community stakeholders. The aspiration is to inform and inspire concrete application of transdisciplinary and participatory methods in concert to address complex socio-environmental challenges.

In Chile, the number of migrants has increased, notably Haitian women who face discrimination and racism, affecting their mental health and occupational performance. Method: A phenomenological and qualitative approach with a descriptive design was employed, using semi-structured interviews for data collection. States must rethink their actions to protect the Human Rights of migrants (Gutiérrez et al., 2020), who, in addition to adapting to new environments and facing the lack of protection laws, suffer discrimination, racism and xenophobia, which negatively affects their mental health. (2010), mention that occupations are an agent that promotes well-being and health, which prevents the emergence of diseases and deficits, promotes physical, psychological and social well-being. [...]the person and the occupation have a close relationship, with occupation being understood as an intrinsic aspect of the human being (Schliebener Tobar, 2020).

Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. NCT04375098.

Background Human bone marrow-derived mesenchymal stem/stromal cells (hBM MSCs) have multiple functions, critical for skeletal formation and function. Their functional heterogeneity, however, represents a major challenge for their isolation and in developing potency and release assays to predict their functionality prior to transplantation. Additionally, potency, biomarker profiles and defining mechanisms of action in a particular clinical setting are increasing requirements of Regulatory Agencies for release of hBM MSCs as Advanced Therapy Medicinal Products for cellular therapies. Since the healing of bone fractures depends on the coupling of new blood vessel formation with osteogenesis, we hypothesised that a correlation between the osteogenic and vascular supportive potential of individual hBM MSC-derived CFU-F (colony forming unit-fibroblastoid) clones might exist. Methods We tested this by assessing the lineage (i.e. adipogenic (A), osteogenic (O) and/or chondrogenic (C)) potential of individual hBM MSC-derived CFU-F clones and determining if their osteogenic (O) potential correlated with their vascular supportive profile in vitro using lineage differentiation assays, endothelial-hBM MSC vascular co-culture assays and transcriptomic (RNAseq) analyses. Results Our results demonstrate that the majority of CFU-F (95%) possessed tri-lineage, bi-lineage or uni-lineage osteogenic capacity, with 64% of the CFU-F exhibiting tri-lineage AOC potential. We found a correlation between the osteogenic and vascular tubule supportive activity of CFU-F clones, with the strength of this association being donor dependent. RNAseq of individual clones defined gene fingerprints relevant to this correlation. Conclusions This study identified a donor-dependent correlation between osteogenic and vascular supportive potential of hBM MSCs and important gene signatures that support these functions that are relevant to their bone regenerative properties.

To determine whether time-to-intubation was associated with higher ICU mortality in patients with COVID-19 on mechanical ventilation due to respiratory insufficiency. We conducted an observational, prospective, single-center study of patients with confirmed SARS-CoV-2 infection hospitalized with moderate to severe ARDS, connected to mechanical ventilation in the ICU between March 17 and July 31, 2020. We examined their general and clinical characteristics. Time-to-intubation was the time from hospital admission to endotracheal intubation. We included 183 consecutive patients; 28% were female, and median age was 62 years old. Eighty-eight patients (48%) were intubated before 48 h (early) and ninety-five (52%) after 48 h (late). Patients intubated early had similar admission PaO2/FiO2 ratio (123 vs 99; p = 0.179) but were younger (59 vs 64; p = 0.013) and had higher body mass index (30 vs 28; p = 0.006) compared to patients intubated late. Mortality was higher in patients intubated late (18% versus 43%), with admission PaO2/FiO2 ratio < 100 mmHg (OR 5.2; p = 0.011), of older age (OR 1.1; p = 0.001), and with previous use of ACE inhibitors (OR 4.8; p = 0.026). In COVID-19 patients, late intubation, Pafi <100, older age, and previous ACE inhibitors use were associated with increased ICU mortality. •Time to intubation maybe associated with an increase in mortality in hypoxemic COVID-19 patients.•COVID-19 patients > 60 years-old, admitted with PaO2FiO2 ratio < 100 may have higher ICU mortality when intubated after 48 h.•Patients admitted with PaO2FiO2 ratio < 100 intubated > 48 h have worse lung mechanics than similar patients intubated < 48 h.

The aim of this research consisted of examining parental socialization taking into account the nature and variability of daily situations. The objectives of this study were: to explore parent´ behavior according to the degree of importance of diverse situations included in the Parental Socialization Scale in Adolescence (ESPA29); and to analyze whether the importance of these situations is associated with parents´ different socialization practices. Using the information provided by experts in family and/or adolescence, responses of 223 adolescents on the ESPA29 were analyzed from dimensional and typological approaches depending on the relevance of the educative situations over which parents have to intervene. Data analysis showed that adolescents perceived their mothers´ behavior differently depending on the importance of daily situations. The need for understanding parental socialization across educative situations is highlighted.

Successful therapies for patients with breast cancer often lose their initial effectiveness. Thus, identifying new molecular targets is a constant goal in the fight against breast cancer. Gpn3 is a protein required for RNA polymerase II nuclear targeting in both yeast and human cells. We investigated here the effect of suppressing Gpn3 expression on cell proliferation in a progression series of isogenic cell lines derived from the nontumorigenic MCF-10A breast cells that recapitulate different stages of breast carcinogenesis. Gpn3 protein levels were comparable in all malignant derivatives of the nontumorigenic MCF-10A cells. shRNA-mediated inhibition of Gpn3 expression markedly decreased cell proliferation in all MCF-10A sublines. A fraction of the largest RNA polymerase II subunit Rpb1 was retained in the cytoplasm, but most Rpb1 remained nuclear after suppressing Gpn3 in all cell lines studied. Long-term proliferation experiments in cells with suppressed Gpn3 expression resulted in the eventual loss of all isogenic cell lines but MCF-10CA1d.cl1. In MCF-10CA1d.cl1 cells, Gpn3 knockdown reduced the proliferation of breast cancer stem cells as evaluated by mammosphere assays. After the identification that Gpn3 plays a key role in cell proliferation in mammary epithelial cells independent of the degree of transformation, we also analyzed the importance of Gpn3 in other human breast cancer cell lines from different subtypes. Gpn3 was also required for cell proliferation and nuclear translocation of RNA polymerase II in such cellular models. Altogether, our results show that Gpn3 is essential for breast cancer cell proliferation regardless of the transformation level, indicating that Gpn3 could be considered a molecular target for the development of new antiproliferative therapies. Importantly, our analysis of public data revealed that Gpn3 overexpression was associated with a significant decrease in overall survival in patients with estrogen receptor-positive and Human epidermal growth factor receptor 2 (HER2+) breast cancer, supporting our proposal that targeting Gpn3 could potentially benefit patients with breast cancer.