[Validation of the COVID-19-12O score for predicting readmissions/revisits in patients with SARS-CoV-2 pneumonia discharged from the emergency department]. / Validación de la escala COVID-19-12O para predecir reingreso/revisita en pacientes con neumonía por SARS-CoV-2 dados de alta desde Urgencias.

Objective: The COVID-19-12O score has been validated for determining the risk of respiratory failure in patients hospitalized due to COVID-19. This study aims to assess whether the score is effective for predicting readmissions and revisits in patients with SARS-CoV-2 pneumonia discharged from a hospital emergency department (HED). Method: This work is a retrospective cohort of consecutive patients with SARS-CoV-2 pneumonia discharged from the HED of a tertiary hospital from January 7 to February 17, 2021. The COVID-19-12O score with a cut-off point of nine points was used to define the risk of admissions or revisits. The primary outcome variable was a revisit with or without hospital readmission after 30 days of discharge from the HED. Results: Seventy-seven patients were included. The median age was 59 years, 63.6% were men, and the Charlson Comorbidity Index was 2. A total of 9.1% had an emergency room revisit and 15.3% had a deferred hospital admission. The relative risk (RR) for an HED revisit was 0.46 (0.04-4.62, 95% CI p = 0.452) and the RR for hospital readmission was 6.88 (1.20-39.49, 95% CI, p < 0.005). Conclusions: The COVID-19-12O score is effective in determining the risk of hospital readmission in patients discharged from an HED with SARS-CoV-2 pneumonia, but is not useful for assessing the risk of revisit.

[Prognosis in elderly patients with falls treated in emergency departments: The EDEN-3 study]. / Pronóstico en pacientes ancianos con caídas atendidos en servicios de urgencias: estudio EDEN-3.

OBJECTIVE: To investigate whether falls in people ≥65 years old are a prognostic factor for adverse events compared to the rest of older patients who consult emergency departments, and identify factors related to a worse long-term evolution. METHOD: EDEN cohort that included patients ≥65 years old. Those patients who consulted for fall and the rest were distinguished. Twelve variables were collected. For comparison: two groups matched by fall propensity score. We compared mortality at one year and combined adverse event post-discharge at one year. In patients with falls, variables independently related to evolution were identified. RESULTS: Two thousand seven hundred and forty-five patients treated for falls and 22,920 for other reasons. Mortality at one year was 14.4% (9.5% vs. 15.0%, respectively, P<.001) and the combined post-discharge adverse event at one year was 60.6% (52.2% vs. 61.7%, respectively, P<.001). In 4748 patients matched by fall propensity score (2372 in each group), the inverse association between consultation for fall and mortality (HR: 0.705, 95% CI: 0.5880.846) and post-discharge combined adverse event (0.758, 0.701-0.820) remained significant. Factors associated with mortality in patients with falls were ≥80 years (2.097, 1.521-2.891) and comorbidity (2.393, 1.574-3.636) while being female was a protective factor (0.758, 0.584-0.985). Between the factors associated with post-discharge combined adverse hospitalization in the index event was a protective factor (0.804, 0.685-0.943). CONCLUSIONS: Patients over 65 years of age treated in the emergency room for falls have a better prognosis. Hospitalization was a protective factor of combined postdischarge adverse event.

Validation of the COVID-19-12O score for predicting readmissions/revisits in patients with SARS-CoV-2 pneumonia discharged from the emergency department.

OBJECTIVE: The COVID-19-12O-score has been validated to determine the risk of respiratory failure in patients hospitalized for COVID-19. Our study aims to assess whether the score is effective in patients with SARS-CoV-2 pneumonia discharged from a hospital emergency department (HED) to predict readmission and revisit. METHOD: Retrospective cohort of patients with SARS-CoV-2 pneumonia discharged consecutively from an HUS of a tertiary hospital, from January 7 to February 17, 2021, where we applied the COVID-19-12O -score, with a cut-off point of 9 points to define the risk of admission or revisit. The primary outcome variable was revisit with or without hospital readmission after 30 days of discharge from HUS. RESULTS: We included 77 patients, with a median age of 59 years, 63.6% men and Charlson index of 2. 9.1% had an emergency room revisit and 15.3% had a deferred hospital admission. The relative risk (RR) for emergency journal was 0.46 (0.04-4.62, 95% CI, p=0.452), and the RR for hospital readmission was 6.88 (1.20-39.49, 95% CI, p<0.005). CONCLUSIONS: The COVID-19-12O -score is effective in determining the risk of hospital readmission in patients discharged from HED with SARS-CoV-2 pneumonia, but is not useful for assessing the risk of revisit.

Prognosis of acute heart failure based on clinical data of congestion.

BACKGROUND AND OBJECTIVES: This work aims to assess whether symptoms/signs of congestion in patients with acute heart failure (AHF) evaluated in hospital emergency departments (HED) allows for predicting short-term progress. PATIENTS AND METHODS: The study group comprised consecutive patients diagnosed with AHF in 45 HED from EAHFE Registry. We collected clinical variables of systemic congestion (edema in the lower extremities, jugular vein distention, hepatomegaly) and pulmonary congestion (dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, and pulmonary crackles) and analysed their individual and group association with all-cause 30-day of mortality crudely and adjusted for differences between groups. RESULTS: We analysed 18,120 patients (median = 83 years, interquartile range [IQR] = 76-88; women = 55.7%). Of them, 44.6% had > 3 congestive symptoms/signs. Individually, the 30-day adjusted risk of death increased 14% for jugular vein distention (hazard ratio [HR] = 1.14, 95% confidence interval [95%CI] = 1.01-1.28) and 96% for dyspnea on exertion (HR = 1.96, 95% CI = 1.55-2.49). Assessed jointly, the risk progressively increased with the number of symptoms/signs present; compared to patients without symptoms/signs of congestion, the risk increased by 109%, 123 %, and 156% in patients with 1-2, 3-5, and 6-7 symptoms/signs, respectively. These associations did not show interaction with the final disposition of the patient after their emergency care (discharge/hospitalization) with the exception of edema in the lower extremities, which had a better prognosis in discharged patients (HR = 0.66, 95% CI = 0.49-0.89) than hospitalised patients (HR = 1.01, 95% CI = 0.65-1.57; interaction p < 0.001). CONCLUSION: The presence of a greater number of congestive symptoms/signs was associated with greater all-cause 30-day mortality. Individually, jugular vein distention and dyspnea on exertion were associated with higher short-term mortality.

[Association between influenza vaccination and mortality due to COVID-19]. / Asociación entre la vacunación contra influenza y la mortalidad por COVID-19.

Background: It has recently been suggested that influenza vaccination may be a factor associated with decreased COVID-19 mortality. Methods: An age-matched case-control study based on hospital cases. We included subjects aged 18 years and older with a diagnosis of moderate to severe COVID-19. Infection was corroborated by RT-PCR test for SARS-COV-2. Deceased subjects were considered cases, controls were patients discharged due to improvement of acute symptoms. We used bivariate analysis to determine factors associated with death from COVID-19, and calculated odds ratios and 95% confidence intervals. Results: A total of 560 patients were included in the study, 214 (38.2%) were considered cases and 346 (61.7%) controls. A significant difference was observed with the presence of type 2 diabetes mellitus [54% vs. 39.3% between cases and controls, respectively (p=.04)] and having received influenza vaccination (p= .02). Type 2 diabetes mellitus was associated with higher COVID-19 mortality [OR 1.8 (95% CI 1.2-2.5) p=.01], whereas having been immunised against influenza in 2019 was associated with lower mortality in this group of patients [OR .6 (95% CI .4-.9) p=.02]. Conclusions: Influenza vaccination in the previous year appears to be associated with lower mortality from COVID-19; whereas type 2 diabetes mellitus is confirmed as a condition associated with higher mortality.

Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death.

Because of its key role in cancer development and progression, STAT3 has become an attractive target for developing new cancer therapeutics. While several STAT3 inhibitors have progressed to advanced stages of development, their underlying biology and mechanisms of action are often more complex than would be expected from specific binding to STAT3. Here, we have identified and optimized a series of compounds that block STAT3-dependent luciferase expression with nanomolar potency. Unexpectedly, our lead compounds did not bind to cellular STAT3 but to another prominent anticancer drug target, TrxR1. We further identified that TrxR1 inhibition induced Prx2 and STAT3 oxidation, which subsequently blocked STAT3-dependent transcription. Moreover, previously identified inhibitors of STAT3 were also found to inhibit TrxR1, and likewise, established TrxR1 inhibitors block STAT3-dependent transcriptional activity. These results provide new insights into the complexities of STAT3 redox regulation while highlighting a novel mechanism to block aberrant STAT3 signaling in cancer cells.

Control of protein function through oxidation and reduction of persulfidated states.

Irreversible oxidation of Cys residues to sulfinic/sulfonic forms typically impairs protein function. We found that persulfidation (CysSSH) protects Cys from irreversible oxidative loss of function by the formation of CysSSO1-3H derivatives that can subsequently be reduced back to native thiols. Reductive reactivation of oxidized persulfides by the thioredoxin system was demonstrated in albumin, Prx2, and PTP1B. In cells, this mechanism protects and regulates key proteins of signaling pathways, including Prx2, PTEN, PTP1B, HSP90, and KEAP1. Using quantitative mass spectrometry, we show that (i) CysSSH and CysSSO3H species are abundant in mouse liver and enzymatically regulated by the glutathione and thioredoxin systems and (ii) deletion of the thioredoxin-related protein TRP14 in mice altered CysSSH levels on a subset of proteins, predicting a role for TRP14 in persulfide signaling. Furthermore, selenium supplementation, polysulfide treatment, or knockdown of TRP14 mediated cellular responses to EGF, suggesting a role for TrxR1/TRP14-regulated oxidative persulfidation in growth factor responsiveness.

Prevalence of labrum and articular cartilage injuries of the hip on 3T magnetic resonance imaging of asymptomatic elite soccer players. / Prevalencia de lesiones del labrum y del cartílago articular de la cadera en imagen por resonancia magnética simple 3 T de futbolistas profesionales asintomáticos.

OBJECTIVE: To establish the prevalence of lesions of the labrum and articular cartilage of the hip in asymptomatic elite soccer players by performing 3T magnetic resonance imaging. METHODS: Eighty-four asymptomatic hips of 42 professional soccer players were evaluated. Male subjects older than 18 years were included. Cam and pincer deformity were defined as an alpha angle greater than 55 degrees and a lateral centre edge angle greater than 39 degrees, respectively. Labral injuries were classified with the Czerny classification and cartilage damage was classified with the Outerbridge classification. Specific statistical tests were used to establish the relationship between anatomical variances of the hip and the presence of chondral and labral injuries. RESULTS: FAI morphology prevalence was 25%. Abnormalities such as cam (22.5%) and labral injuries (33.8%) were found. Those cases with reported labral injury were predominantly intrasubstance damage (18.8%). Anatomical features of FAI were found to be related to lesions of the femoral cartilage (P<.001), chondrolabral damage (P=.042), or both injuries (P<.001). CONCLUSION: Asymptomatic labral or cartilaginous injuries of the hip were reported in 25% of the included professional soccer players. These injuries were associated with anatomical features of FAI.

Identification of galectin-3 and mucin-type O-glycans in breast cancer and its metastasis to brain.

Galectin-3 has been implicated in tumor progression. We demonstrated immunohistochemically that galectin-3 was negative in normal breast tissue, but it was highly increased in breast cancer and in metastatic tissues to brain. Similarly, histochemistry with mucin-specific lectins showed increased recognition in breast tumor and metastasis with Machaerocereus eruca agglutinin (Fualpha 1,2 (GalNAcalpha 1,3) Galss1,4 in complex mucin) but not for Amaranthus leucocarpus (Galss1,3-GalNAc-alpha 1,0-Ser/Thr) and Arachis hypogaea lectins (Galss1,3GalNAc/Galss1,4GlcNAc). Mucin-type glycans and galectin-3 colocalized in breast cancer and metastasis, but not in normal tissue, suggesting upregulated biosynthesis of complex O-glycosidically linked glycans and galectin-3 favor breast cancer progression and brain metastasis.

Comparison of radar data versus rainfall data.

Doppler radar data are increasingly used in rainfall-runoff synthesis studies, perhaps due to radar data availability, among other factors. However, the veracity of the radar data are often a topic of concern. In this paper, three Doppler radar outcomes developed by the United States National Weather Service at three radar sites are examined and compared to actual rain gage data for two separate severe storm events in order to assess accuracy in the published radar estimates of rainfall. Because the subject storms were very intense rainfall events lasting approximately one hour in duration, direct comparisons between the three radar gages themselves can be made, as well as a comparison to rain gage data at a rain gage location subjected to the same storm cells. It is shown that topographic interference with the radar outcomes can be a significant factor leading to differences between radar and rain gage readings, and that care is needed in calibrating radar outcomes using available rain gage data in order to interpolate rainfall estimates between rain gages using the spatial variation observed in the radar readings. The paper establishes and describes•the need for "ground-truthing" of radar data, and•possible errors due to topographic interference.

Altered glycosylation pattern of proteins in Alzheimer disease.

Post-translational modifications due to glycosylation of proteins in human brains from patients with Alzheimer disease (AD) were analyzed using lectin histochemistry. Results indicate a significant increase in the production of O-glycosylated (containing Galbeta1,3GalNAc alpha1,0 Ser/Thr or GalNAc alpha1,0 Ser/Thr) proteins in neuritic plaques and neurofibrillary tangles which are the major histopathological hallmarks of AD brains. These alterations were determined by positive labelling with lectins obtained from Amaranthus leucocarpus (ALL) and Macrobrachium rosenbergii (MRL) respectively. Immunohistochemistry indicated that the lectin-staining labelled specifically both neurofibrillary tangles and neuritic plaques. In contrast, lectins labelling was restricted to microvessels in normal control brains. These results provide evidence that modifications of the specific glycosylation patterns are closely related with the presence of the hallmark lesions of this disease, suggesting that an abnormal enzymatic processing of proteins may be an early event in the neuronal degeneration which characterises AD.

O-Glycosylation in sprouting neurons in Alzheimer disease, indicating reactive plasticity.

Reactive plasticity, including axonal and dendritic sprouting and reactive synaptogenesis, has been proposed to contribute to the pathogenesis of several neurological disorders. This work was aimed at identifying the possible role of protein glycosylation in the brain from patients with Alzheimer disease (AD), using lectin histochemistry, as determinants of reactive plasticity. Results indicate an increase in the production of cryptic O-glycosidically linked proteins (NeuAcalpha2,6 Galbeta1,3GalNAcalpha1,0 Ser/Thr or sialyl-T-antigen) in neuritic sprouting in AD brains as determined by positive labeling with Amaranthus leucocarpus (ALL, T-antigen-specific) and Macrobrachium rosenbergii (MRL, specific for NeuAc5,9Ac2) lectins. Immunohistochemistry indicated that lectin staining was specific for the synaptic sprouting process (meganeurites) in AD. These results were confirmed using anti-synaptophysin and anti-GAP 43 antibodies, which recognized meganeurites and dystrophic neurites around amyloid-beta deposits. In normal control brains, labeling with the aforementioned lectins was restricted to microvessels. Control experiments with neuraminidase-treated brain samples revealed positivity to the lectin from Arachis hypogaea (PNA), which is specific for galactose. Our results suggest specific O-glycosylation patterns of proteins closely related to neuronal plasticity in AD.

Coexistence of reactive plasticity and neurodegeneration in Alzheimer diseased brains.

Alzheimer's disease (AD) is a pathological process characterized by neuron degeneration and, as recently suggested, brain plasticity. In this work, we compared the reactive plasticity in AD brains associated to O-glycosydically linked glycans, recognized by lectins from Amaranthus leucocarpus (ALL) and Macrobrachium rosenbergii (MRL), and the tau neuritic degeneration. The neuritic degenerative process was evaluated by the quantification of aggregated neuritic structures. Lesions were determined using antibodies against hyperphosphorylated-tau (AD2), amyloid-beta, and synaptophysin. In these conditions, we classified and quantified three pathological structures associated to the neuritic degenerative process: 1) Amyloid-beta deposits (AbetaDs), 2) Classic neuritic plaques (NPs), and 3) Dystrophic neurites clusters (DNCs) lacking amyloid-beta deposits. Reactive plasticity structures were constituted by meganeuritic clusters (MCs) and peri-neuronal sprouting in neurons of the CA4 region of the hippocampus, immunoreactive to synaptophysin (exclusively in AD brains) and GAP-43. Besides, MCs were associated to sialylated O-glycosydically linked glycans as determined by positive labeling with ALL and MRL. Considering that these lectins are specific for the synaptic sprouting process in AD, our results suggest the co-occurrence of of several areas of reactive plasticity and neuron degeneration in AD.

NeuAc alpha 2,3gal-glycoconjugate expression determines cell susceptibility to the porcine rubulavirus LPMV.

Relevance of membrane sialoglycoconjugates as receptors for infection by the porcine rubulavirus has been determined in vitro by sugar and lectin competition assays and by inhibition of glycosylation. Our results show that NeuAc alpha 2,3Gal but not NeuAc alpha 2,6Gal inhibits the virus infectivity of Vero cells, and the virus was effectively blocked with the lectin Maackia amurensis, specific for NeuAc alpha 2,3Gal. Inhibition of the cellular glycosylation with tunicamycin, deoxinojirimycin as well as neuraminidase treatment diminishes the viral capacity to bind and infect this cell line. Dexamethasone, which promotes the activity of sialyl alpha 2,6 glycosyltransferase, also diminishes the cell susceptibility for infection. This is the first report confirming that NeuAc alpha-2,3Gal recognition is determinant in the pathogenesis of the porcine rubulavirus.

Adjuvant surgical and hormonal treatment of leiomyomatosis peritonealis disseminata. A case report.

Leiomyomatosis peritonealis disseminata (LPD) is a rare condition that usually presents during pregnancy or in women during the reproductive years and who are taking oral contraceptives. An unusual case of extensive LPD occurred in a 39-year-old woman who was not pregnant and had never taken oral contraceptives. The condition was treated successfully with total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, limited debulking and adjuvant hormonal therapy with megestrol acetate. Complete, rapid remission of residual tumor occurred in two months, as substantiated by clinical examination and serial sonography and laparoscopy. This is the first time that adjuvant hormonal therapy has been used successfully in the treatment of LPD. Radical surgery in patients with LPD is probably not indicated, and the use of adjuvant hormonal therapy may accelerate regression of residual tumor. Further evaluation of this form of therapy is recommended.

[Acute human immunodeficiency virus infection associated with facial diplegia]. / Infección aguda por el virus de la inmunodeficiencia humana asociada a diplejia facial.

We describe the case of a 21-year-old parenterally drug-addict man, who presented an acute and self-limited disease, temporarily associated to seroconversion against the human immunodeficiency virus. During his evolution, the patient developed aseptic meningitis and facial diplegia. Two lymphatic ganglions were histopathologically and sequentially studied during the third and sixth week of the disease, showing an intense follicular depletion in the first sample, which reverted towards a pattern of follicular hyperplasia in the second one.

Variation of saponin contents and physiological status in Quillaja saponaria under different environmental conditions.

Quillaja saponaria (Quillay), an evergreen tree found in Chile, is one of the main sources of saponins. Quillaja saponins have hypocholesterolaemic, anticarcinogenic, antioxidant and pesticidal properties, and are used as adjuvants for vaccines. Samples of Quillay growing at three zones in O'Higgins Region, Chile (Coastal, Central and Mountain zones) were analyzed for content of saponins and physiological status. The results revealed differences in the content of saponins depending on the zone of sample collection. The highest contents were found in samples from the Mountain zone, where the highest saponin contents were accompanied by the lowest foliar nitrogen contents, the highest antioxidant activity and the highest carotenoid contents. The results suggest a physiological and adaptive mechanism of saponins in plants to survive under unfavourable environmental conditions. The results have important implications for a theoretical basis for the design of a reasonable harvest, to avoid the cost of poor quality material, and also to provide a sustainable use and conservation of this important species. Further research on the effects of stress will improve our understanding of the saponins production and their physiological functions in plants, whereas they have generally been studied for their biological and chemical applications.

Identification of a large cluster of coiled coil-nucleotide binding site--leucine rich repeat-type genes from the Rps1 region containing Phytophthora resistance genes in soybean.

Fifteen Rps genes confer resistance against the oomycete pathogen Phytophthora sojae, which causes root and stem rot disease in soybean. We have isolated a disease resistance gene-like sequence from the genomic region containing Rps1-k. Four classes of cDNA of the sequence were isolated from etiolated hypocotyl tissues that express the Rps1-k-encoded Phytophthora resistance. Sequence analyses of a cDNA clone showed that the sequence is a member of the coiled coil-nucleotide binding site-leucine rich repeat (CC-NBS-LRR)-type of disease resistance genes. It showed 36% identity to the recently cloned soybean resistance gene Rpg1-b, which confers resistance against Pseudomonas syringae pv. glycinea, and 56% and 38% sequence identity to putative resistance gene sequences from lotus and Medicago truncatula, respectively. The soybean genome contains about 38 copies of the sequence. Most of these copies are clustered in approximately 600 kb of contiguous DNA of the Rps1-k region. We have identified a recombinant that carries both rps1-k- and Rps1-k-haplotype-specific allelomorphs of two Rps1-k-linked molecular markers. An unequal crossover event presumably led to duplication of alleles for these two physically linked molecular markers. We hypothesize that the unequal crossing over was one of the mechanisms involved in tandem duplication of CC-NBS-LRR sequences in the Rps1-k region.