Adding vortexing to the Maki technique provides no benefit for the diagnosis of catheter colonization or catheter-related bacteremia.

BACKGROUND: A previous study compared vortexing and Maki techniques for the diagnosis of catheter-related bloodstream infection (CRBSI), and concluded that vortexing was not superior to Maki method. AIM: To determine whether the combined use of vortexing and Maki techniques provides profitability versus the Maki technique for the diagnosis of catheter tip colonization (CTC) and CRBSI. METHODS: Observational and prospective study carried out in an Intensive Care Unit. Patients with suspected catheter-related infection (CRI) and with one central venous catheter for at least 7 days were included. The area under the curve (AUC) of the Maki technique, the vortexing technique and the combination of both techniques for the diagnosis of CTC and CRBSI were compared. RESULTS: We included 136 episodes of suspected CRI. We found 21 cases of CTC of which 10 were also CRBSI cases. Of the 21 CTC episodes, 18 (85.7%) were diagnosed by Maki technique and vortexing technique, 3 (14.3%) only by the technique of Maki, and none only by technique of vortexing. Of the 10 CRBSI episodes, 9 (90.0%) were diagnosed by the techniques of Maki and vortexing, 1 (10.0%) was diagnosed only by the technique of Maki, and none only by the technique of vortexing. We no found differences in the comparison of AUC between the technique of Maki and the combination of Maki and vortexing techniques for the diagnosis of CTC (P = 0.99) and CRBSI (P = 0.99). CONCLUSION: The novel finding of our study was that the combined use of vortexing and Maki techniques did not provide profitability to the technique of Maki alone to CRBSI diagnosis of.

SLESIS-R: an improved score for prediction of serious infection in patients with systemic lupus erythematosus based on the RELESSER prospective cohort.

OBJECTIVE: To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. METHODS: We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. RESULTS: A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777-0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. CONCLUSIONS: SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures.

Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients.

OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

A Family with EEC Syndrome in the Son and ADULT Syndrome in His Father Caused by the c.797G>A (p.Arg266Gln) Pathogenic Variant in the TP63 Gene.

Introduction: To our knowledge, there are few examples of intrafamilial variability involving two different TP63-linked morphopathies within a same family. Here, we describe a Mexican family in which the son had ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3), and his father acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome, both heterozygous for the p.Arg266Gln pathogenic variant in TP63. Additionally, we reviewed the clinical information reported for this TP63 genotype. Case Presentation: The son of this family presented ectodermal defects (thin and sparse hair, mild nail dysplasia), tetramelic ectrodactyly, syndactyly, and nasolacrimal duct obstruction (NLDO), indicative of an EEC3 diagnosis. His father, however, exhibited severe NLDO, facial freckling, dental abnormalities, mild nail dysplasia, and a history of micturition problems, compatible with ADULT syndrome. Both were heterozygous for the NM_003722.5(TP63):c.797G>A (p.Arg266Gln) pathogenic variant in TP63. Discussion: This report expands the spectrum of intrafamilial variability confirming that this can include the expression of distinct types of TP63-related disorders among different members of the same family, whose implications should be also considered in genetic counseling. From our review, we observed that p.Arg266Gln variant seems to correlate particularly with the presence of NLDO, sparse hair/eyebrows, ridged/dystrophic nails, anodontia/hypodontia, and micturition difficulties, as well as for a minor frequency of cleft lip/cleft palate.

Parallel algorithm for discovering and comparing three-dimensional proteins patterns.

Identifying conserved (similar) three-dimensional patterns among a set of proteins can be helpful for the rational design of polypharmacological drugs. Some available tools allow this identification from a limited perspective, only considering the available information, such as known binding sites or previously annotated structural motifs. Thus, these approaches do not look for similarities among all putative orthosteric and or allosteric bindings sites between protein structures. To overcome this tech-weakness Geomfinder was developed, an algorithm for the estimation of similarities between all pairs of three-dimensional amino acids patterns detected in any two given protein structures, which works without information about their known patterns. Even though Geomfinder is a functional alternative to compare small structural proteins, it is computationally unfeasible for the case of large protein processing and the algorithm needs to improve its performance. This work presents several parallel versions of the Geomfinder to exploit SMPs, distributed memory systems, hybrid version of SMP and distributed memory systems, and GPU based systems. Results show significant improvements in performance as compared to the original version and achieve up to 24.5x speedup when analyzing proteins of average size and up to 95.4x in larger proteins.

Comparative Study of Predictive Models for the Detection of Patients at High Risk of Inadequate Colonic Cleansing.

Background: Various predictive models have been published to identify outpatients with inadequate colonic cleansing who may benefit from intensified preparations to improve colonoscopy quality. The main objective of this study was to compare the accuracy of three predictive models for identifying poor bowel preparation in outpatients undergoing colonoscopy. Methods: This cross-sectional study included patients scheduled for outpatient colonoscopy over a 3-month period. We evaluated and compared three predictive models (Models 1-3). The quality of colonic cleansing was assessed using the Boston Bowel Preparation Scale. We calculated the area under the curve (AUC) and the corresponding 95% confidence interval for each model. Additionally, we performed simple and multiple logistic regression analyses to identify variables associated with inadequate colonic cleansing and developed a new model. Results: A total of 649 consecutive patients were included in the study, of whom 84.3% had adequate colonic cleansing quality. The AUCs of Model 1 (AUC = 0.67, 95% CI [0.63-0.70]) and Model 2 (AUC = 0.62, 95% CI [0.58-0.66]) were significantly higher than that of Model 3 (AUC = 0.54, 95% CI [0.50-0.58]; p < 0.001). Moreover, Model 1 outperformed Model 2 (p = 0.013). However, the new model did not demonstrate improved accuracy compared to the older models (AUC = 0.671). Conclusions: Among the three compared models, Model 1 showed the highest accuracy for predicting poor bowel preparation in outpatients undergoing colonoscopy and could be useful in clinical practice to decrease the percentage of inadequately prepared patients.

Agreement between the perception of colon cleansing reported by patients and colon cleansing assessed by a validated colon cleansing scale.

AIMS: Patients' perception of their cleansing quality can guide strategies to improve cleansing during colonoscopy. There are no studies assessing the agreement between the quality of cleansing perceived by patients and cleansing quality assessed during colonoscopy using validated bowel preparation scales. The main aim of this study was to compare the cleansing quality reported by patients with the quality during colonoscopy using the Boston Bowel Preparation Scale (BBPS). PATIENTS AND METHODS: Consecutive patients referred to an outpatient colonoscopy were included. Four drawings representing different degrees of cleansing were designed. Patients chose the drawing that most resembled the last stool. The predictive ability of the patient's perception and agreement between the patient's perception and the BBPS were calculated. A BBPS score of <2 points in any segment was considered inadequate. RESULTS: Six hundred and thirty-three patients were included (age: 62.8±13.7 years, male: 53.4%). Overall, 107 patients (16.9%) had inadequate cleansing during colonoscopy, and in 12.2% of cases, the patient's perception was poor. The patient's perception compared to the quality of cleanliness during colonoscopy presented a positive and negative predictive value of 54.6% and 88.3%, respectively. The agreement between patient perception and the BBPS was significant (P<0.001), although fair (k=0.37). The results were similar in a validation cohort of 378 patients (k=0.41). CONCLUSIONS: The cleanliness perceived by the patient and the quality of cleanliness using a validated scale were correlated, although fair. However, this measure satisfactorily identified patients with adequate preparation. Cleansing rescue strategies may target patients who self-report improper cleaning. Registration number of the trial: NCT03830489.

Oxide nanoparticles based in magnesium as a potential dental tool to inhibit bacterial activity and promote osteoblast viability.

Functional nano-fillers are commonly used to reduce bacterial colonization in dentistry. This study aimed to synthesize, characterize, and evaluate the biological effects of magnesium oxide (MgO) nanoparticles (NP) obtained by mechanosynthesis. XRD, TEM, FT-IR, and UV-Vis were used to characterize MgO-NP which were subsequently tested for their activity against Staphylococcus aureus, Enterococcus faecalis and Escherichia coli (E. coli). The effects of MgO-NP on osteoblast cells were also analyzed. Three variables were studied: microbial inhibition by optical density (OD; 570-nm), viability estimated by colony-forming-units, and cell proliferation. The characterization of NP is consistent with nanostructures, minimum inhibitory concentration between 1.5-5 mg/mL, and microbial inhibition at 9.75 ug/mL concentration for E. coli were determined. There were different concentration-dependent effects on cell proliferation. Results were observed with 0.156 mg/mL MgO-NP, which increased cell proliferation at 24 and 48 h. The results suggest the antibacterial suitability of MgO-NP, with tolerable viability of mammalian cells for dental applications.

Antibacterial and Cytotoxic Study of Hybrid Films Based on Polypropylene and NiO or NiFe2O4 Nanoparticles.

This study presents an in vitro analysis of the bactericidal and cytotoxic properties of hybrid films containing nickel oxide (NiO) and nickel ferrite (NiFe2O4) nanoparticles embedded in polypropylene (PP). The solvent casting method was used to synthesize films of PP, PP@NiO, and PP@NiFe2O4, which were characterized by different spectroscopic and microscopic techniques. The X-ray diffraction (XRD) patterns confirmed that the small crystallite sizes of NiO and NiFe2O4 NPs were maintained even after they were incorporated into the PP matrix. From the Raman scattering spectroscopy data, it was evident that there was a significant interaction between the NPs and the PP matrix. Additionally, the Scanning Electron Microscopy (SEM) analysis revealed a homogeneous dispersion of NiO and NiFe2O4 NPs throughout the PP matrix. The incorporation of the NPs was observed to alter the surface roughness of the films; this behavior was studied by atomic force microscopy (AFM). The antibacterial properties of all films were evaluated against Pseudomonas aeruginosa (ATCC®: 43636™) and Staphylococcus aureus (ATCC®: 23235™), two opportunistic and nosocomial pathogens. The PP@NiO and PP@ NiFe2O4 films showed over 90% bacterial growth inhibition for both strains. Additionally, the effects of the films on human skin cells, such as epidermal keratinocytes and dermal fibroblasts, were evaluated for cytotoxicity. The PP, PP@NiO, and PP@NiFe2O4 films were nontoxic to human keratinocytes. Furthermore, compared to the PP film, improved biocompatibility of the PP@NiFe2O4 film with human fibroblasts was observed. The methodology utilized in this study allows for the production of hybrid films that can inhibit the growth of Gram-positive bacteria, such as S. aureus, and Gram-negative bacteria, such as P. aeruginosa. These films have potential as coating materials to prevent bacterial proliferation on surfaces.

Parthanatos type programmed cell death and septic patient mortality / Muerte celular programada tipo Parthanatos y mortalidad de los pacientes sépticos

Objective: Parthanatos is a form of programmed cell death mediated by apoptosis-inducing factor (AIF). However, there are not data on parthanatos in septic patients. The objective of the current study was to explore whether parthanatos is associated with mortality of septic patients. Design: Observational and prospective study. Setting: Three Spanish Intensive Care Units during 2017. Patients: Patients with sepsis according to Sepsis-3 Consensus criteria. Interventions: Serum AIF concentrations were determined at moment of sepsis diagnosis. Main variable of interest: Mortality at 30 days. Results: There were included 195 septic patients, and non-surviving (n=72) had serum AIF levels (p<0.001), lactic acid (p<0.001) and APACHE-II (p<0.001) that surviving (n=123). Multiple logistic regression analysis showed that patients with serum AIF levels>55.6ng/mL had higher mortality risk (OR=3.290; 95% CI=1.551−6.979; p=0.002) controlling for age, SOFA and lactic acid. Conclusions: Parthanatos is associated with mortality of septic patients. (AU)

Objetivo: Parthanatos es un tipo de muerte celular programada mediada por el factor inductor de apoptosis (AIF). Sin embargo, no hay datos sobre Parthanatos en pacientes sépticos. Por ello, el objetivo de este estudio fue explorar si Parthanatos está asociado con la morlaidad de los pacientes sépticos. Diseño: Estudio observacional y prospective. Ámbito: Tres Unidades de Cuidados Intensivos españolas durante 2017. Pacientes: Pacientes con sepsis en base a los criterios del Consenso Sepsis-3. Intervenciones: Se determinaron las concentraciones séricas de AIF en el momento del diagnóstico de la sepsis. Variable de interés principal: Mortalidad a los 30 días. Resultados: Se incluyeron 195 pacientes sépticos, y los que fallecieron (n=72) presentaron mayores concentraciones séricas de AIF (p<0.001) y de ácido láctico (p<0.001), y mayor puntuación APACHE-II (p<0.001) que los pacientes supervivientes (n=123). El análisis de regresión logística múltiple mostró que los pacientes con concentraciones séricas de AIF>55.6ng/mL tuvieron mayor riesgo de fallecer (OR=3.290; 95% CI=1.551−6.979; p=0.002) controlando por edad, SOFA y ácido láctico. Conclusiones: Parthanatos está asociado con la mortalidad de pacientes sépticos. (AU)

Design and validation of an artificial intelligence system to detect the quality of colon cleansing before colonoscopy.

BACKGROUND AND AIMS: Patients' perception of their bowel cleansing quality may guide rescue cleansing strategies before colonoscopy. The main aim of this study was to train and validate a convolutional neural network (CNN) for classifying rectal effluent during bowel preparation intake as "adequate" or "inadequate" cleansing before colonoscopy. PATIENTS AND METHODS: Patients referred for outpatient colonoscopy were asked to provide images of their rectal effluent during the bowel preparation process. The images were categorized as adequate or inadequate cleansing based on a predefined 4-picture quality scale. A total of 1203 images were collected from 660 patients. The initial dataset (799 images), was split into a training set (80%) and a validation set (20%). The second dataset (404 images) was used to develop a second test of the CNN accuracy. Afterward, CNN prediction was prospectively compared with the Boston Bowel Preparation Scale (BBPS) in 200 additional patients who provided a picture of their last rectal effluent. RESULTS: On the initial dataset, a global accuracy of 97.49%, a sensitivity of 98.17% and a specificity of 96.66% were obtained using the CNN model. On the second dataset, an accuracy of 95%, a sensitivity of 99.60% and a specificity of 87.41% were obtained. The results from the CNN model were significantly associated with those from the BBPS (P<0.001), and 77.78% of the patients with poor bowel preparation were correctly classified. CONCLUSION: The designed CNN is capable of classifying "adequate cleansing" and "inadequate cleansing" images with high accuracy.

Supercritical impregnation of starch aerogels with quercetin: Fungistatic effect and release modelling with a compartmental model.

This work proposes the use of supercritical CO2 to impregnate starch (potato and corn) aerogels with quercetin for a potential fungistatic application. Starch aerogels were successfully produced with supercritical drying, but different results were found depending on the amylose/amylopectin ratio. A higher amount of amylose increases aerogels' specific surface area (with a structure with nanofibrils and nodes) due to the linear and amorphous character of this polymer, whereas a higher amount of amylopectin decreases this property until values of only 25 m2·g-1, obtaining an aerogel with a rough surface. These results were explained with XRD, thermogravimetric, and rheological results (triple step with two temperature sweeps and a time sweep and steady state analysis) concerning hydrogel formation. In fact, retrogradation step plays a more important role in hydrogel formation for a starch source with a higher amount of amylopectin due to an increase in the different polymers' interactions. Supercritical impregnation of quercetin on the aerogels was successfully performed (a loading around 0.30 % with respect to the amount of polymer), and in vitro results indicated that the aerogels produced a fungistatic effect on different types of fungi, but only in the first 12 h because the microorganisms adapted to the surrounding environment. Finally, a compartmental model was used to fit the drug release, which is controlled by quercetin aqueous solubility, indicating the main mass transfer resistances (mass transfer through aerogels was always around 500 min-1 and dissolution process mass transfer from 5·10-3 to 1.65·10-3 s-1) and how an increase in the specific surface area of the aerogels (in the case of corn aerogel) provided a stronger initial burst (70-80 % in 20 min). In fact, this initial burst release was mathematically related to a parameter, that varies from 0.178 to 0.036 depending on the aerogel composition. This study shows that starch aerogels can be impregnated with a hydrophobic compound with fungistatic effect by using supercritical CO2, modifying in addition the drug release by changing the native starch.

Vitamin D deficiency and SARS­CoV­2 infection: A retrospective case-Control study with big-data analysis covering March 2020 to March 2021.

BACKGROUND: Vitamin D may have immunomodulatory functions, and might therefore play a role in the pathogenesis of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no conclusive evidence exists regarding its impact on the prevalence of this infection, the associated course of disease, or prognosis. OBJECTIVE: To study the association between SARS-CoV-2 infection and vitamin D deficiency in patients attending a tertiary university hospital, and to examine the clinical course of infection and prognosis for these patients. METHODS: This non-interventional, retrospective study, which involved big-data analysis and employed artificial intelligence to capture data from free text in the electronic health records of patients diagnosed with SARS-CoV-2, was undertaken at a tertiary university hospital in Madrid, Spain, between March 2020 and March 2021. The variables recorded were vitamin D deficiency, sociodemographic and clinical characteristics, course of disease, and prognosis. RESULTS: Of the 143,157 patients analysed, 36,261 had SARS-CoV-2 infection (25.33%) during the study period, among whom 2,588 (7.14%) had a vitamin D deficiency. Among these latter patients, women (OR 1.45 [95%CI 1.33-1.57]), adults over 80 years of age (OR 2.63 [95%CI 2.38-2.91]), people living in nursing homes (OR 2.88 [95%CI 2.95-3.45]), and patients with walking dependence (OR 3.45 [95%CI 2.85-4.26]) appeared in higher proportion. After adjusting for confounding factors, a higher proportion of subjects with SARS-CoV-2 plus vitamin D deficiency required hospitalisation (OR 1.38 [95%CI 1.26-1.51]), and had a longer mean hospital stay (3.94 compared to 2.19 days in those with normal levels; P = 0.02). CONCLUSION: A low serum 25(OH) vitamin D concentration in patients with SARS-CoV-2 infection is significantly associated with a greater risk of hospitalisation and a longer hospital stay. Among such patients, higher proportions of institutionalised and dependent people over 80 years of age were detected.

Continuous time recurrent neural networks: Overview and benchmarking at forecasting blood glucose in the intensive care unit.

OBJECTIVE: Blood glucose measurements in the intensive care unit (ICU) are typically made at irregular intervals. This presents a challenge in choice of forecasting model. This article gives an overview of continuous time autoregressive recurrent neural networks (CTRNNs) and evaluates how they compare to autoregressive gradient boosted trees (GBT) in forecasting blood glucose in the ICU. METHODS: Continuous time autoregressive recurrent neural networks (CTRNNs) are a deep learning model that account for irregular observations through incorporating continuous evolution of the hidden states between observations. This is achieved using a neural ordinary differential equation (ODE) or neural flow layer. In this manuscript, we give an overview of these models, including the varying architectures that have been proposed to account for issues such as ongoing medical interventions. Further, we demonstrate the application of these models to probabilistic forecasting of blood glucose in a critical care setting using electronic medical record and simulated data and compare with GBT and linear models. RESULTS: The experiments confirm that addition of a neural ODE or neural flow layer generally improves the performance of autoregressive recurrent neural networks in the irregular measurement setting. However, several CTRNN architecture are outperformed by a GBT model (Catboost), with only a long short-term memory (LSTM) and neural ODE based architecture (ODE-LSTM) achieving comparable performance on probabilistic forecasting metrics such as the continuous ranked probability score (ODE-LSTM: 0.118 ± 0.001; Catboost: 0.118 ± 0.001), ignorance score (0.152 ± 0.008; 0.149 ± 0.002) and interval score (175 ± 1; 176 ± 1). CONCLUSION: The application of deep learning methods for forecasting in situations with irregularly measured time series such as blood glucose shows promise. However, appropriate benchmarking by methods such as GBT approaches (plus feature transformation) are key in highlighting whether novel methodologies are truly state of the art in tabular data settings.

Clustering of systemic lupus erythematosus mortality in southwestern Spain.

OBJECTIVE: To analyse time trends in systemic lupus erythematosus (SLE) mortality and explore possible provincial clustering of SLE mortality in Spain (2001-2020). METHODS: We conducted an ecological study using deaths registered in SLE at the Spanish National Institute of Statistics between 2001 and 2020. Jointpoint regression models have been used to evaluate temporal trends. To analyse the spatial pattern of SLE mortality in men and women in Spain, crude rates, age-standardised mortality rates (ASMRs), smooth relative risk (RR) and posterior probabilities (PP) for RR greater than one for the period 2001-2020 were calculated. The Global Moran I index was used to assess the existence of global spatial autocorrelation. Local indicators of spatial association (LISA) and Kulldorff's spatial scan statistic were used to identify clusters. RESULTS: Over the 20 years analyzed in this study, the SLE average ASMR for the period was 2.7 for women and 0.7 for men, with a sex ratio (female/male) of 3.8. In men, no province showed a RR>1. Conversely, in women, eight provinces showed values of RR> 1 with a PP greater than 0.8 (Seville, Cadiz, Huelva and Murcia in the south, Barcelona, Zaragoza, Huesca and Leon in the north). In men, neither of the two methods detected a clustering of provinces. However, in women, both methods identified a cluster of provinces located in the southwest of the country (Huelva, Cádiz, Seville and Malaga) as a cluster with significant excess mortality. In the second cluster (centred on the province of Huelva) obtained with the Kulldorff method, two more provinces were added (Badajoz and Cordoba, also located in the southwest). CONCLUSIONS: We detected a cluster of provinces with an excess risk of female SLE mortality in the southwest of Spain.

Parthanatos type programmed cell death and septic patient mortality.

OBJECTIVE: Parthanatos is a form of programmed cell death mediated by apoptosis-inducing factor (AIF). However, there are not data on parthanatos in septic patients. The objective of the current study was to explore whether parthanatos is associated with mortality of septic patients. DESIGN: Observational and prospective study. SETTING: Three Spanish Intensive Care Units during 2017. PATIENTS: Patients with sepsis according to Sepsis-3 Consensus criteria. INTERVENTIONS: Serum AIF concentrations were determined at moment of sepsis diagnosis. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: There were included 195 septic patients, and non-surviving (n=72) had serum AIF levels (p<0.001), lactic acid (p<0.001) and APACHE-II (p<0.001) that surviving (n=123). Multiple logistic regression analysis showed that patients with serum AIF levels>55.6ng/mL had higher mortality risk (OR=3.290; 95% CI=1.551-6.979; p=0.002) controlling for age, SOFA and lactic acid. CONCLUSIONS: Parthanatos is associated with mortality of septic patients.

Ultrafast fluorescence depolarisation in green fluorescence protein tandem dimers as hydrophobic environment sensitive probes.

Advances in ultra-fast photonics have enabled monitoring of biochemical interactions on a sub nano-second time scale. In addition, picosecond dynamics of intermolecular energy transfer in fluorescent proteins has been observed. Here, we present the development of a genetically encoded fluorescent sensor that can detect changes in hydrophobicity by monitoring ultrafast fluorescence depolarisation. Our sensor is composed of a pair of dimeric enhanced green fluorescent proteins (dEGFPs) linked by a flexible amino-acid linker. We show dimerisation is perturbed by the addition of glycerol which interferes with the hydrophobic interaction of the two proteins. Time-resolved fluorescence anisotropy revealed a systematic attenuation of ultrafast fluorescence depolarisation when the sensor was exposed to increasing glycerol concentrations. This suggests that as hydrophobicity increases, dEGFP pairing decreases within a tandem dimer. Un-pairing of the protein fluorophores dramatically alters the rate of energy transfer between the proteins, resulting in an increase in the limiting anisotropy of the sensor.

Elevated soluble fas blood concentrations in patients dying from spontaneous intracerebral hemorrhage.

BACKGROUND: Several studies of spontaneous intracerebral hemorrhage (SICH) patients have shown apoptotic changes in brain samples after hematoma evacuation. However, there have been no data on the association between blood concentrations of soluble fas (sFas) (the main surface death receptor of the extrinsic apoptosis pathway) and the prognosis of spontaneous intracranial hypotension (SIH) patients. AIM: To determine whether there is an association between blood sFas concentrations and SICH patient mortality. METHODS: We included patients with severe and supratentorial SIH. Severe was defined as having Glasgow Coma Scale < 9. We determined serum sFas concentrations at the time of severe SICH diagnosis. RESULTS: We found that non-surviving patients (n = 36) compared to surviving patients (n = 39) had higher ICH score (P = 0.001), higher midline shift (P = 0.004), higher serum sFas concentrations (P < 0.001), and lower rate of early hematoma evacuation (P = 0.04). Multiple logistic regression analysis showed an association between serum sFas concentrations and 30-d mortality (odds ratio = 1.070; 95% confidence interval = 1.014-1.129; P = 0.01) controlling for ICH score, midline shift, and early hematoma evacuation. CONCLUSION: The association of blood sFas concentrations and SICH patient mortality is a novel finding in our study.