Inconsistency Between Pictures on Baby Diaper Packaging in Europe and Safe Infant Sleep Recommendations.

OBJECTIVE: To describe the level of inconsistency between pictures on baby diaper packaging and safe infant sleep recommendations (SISRs) in Europe. STUDY DESIGN: We attempted to identify all packaging of baby diapers sold in 11 European countries for infants weighing less than 5 kg through internet searches from July 2022 through February 2023. For each type of package, we extracted whether there was a picture depicting a baby, whether the baby was sleeping, and whether the picture of the sleeping baby was inconsistent with ≥1 of 3 SISRs: (i) nonsupine sleeping position, (ii) soft objects or loose bedding, or (iii) sharing a sleep surface with another person. Data were aggregated at the country level, and a random-effects meta-analysis of proportions was used to obtain summary estimates. The outcome was the summary estimate of the proportion of pictures that were inconsistent with SISRs. RESULTS: We identified 631 baby diaper packaging types of which 49% (95% CI: 42-57; n = 311) displayed a picture of a sleeping baby. Among those 311 packages, 79% (95% CI 73-84) were inconsistent with ≥1 SISR, including a nonsupine sleeping position, 45% (95% CI 39-51), soft objects or loose bedding such as pillows or blankets, 51% (95% CI 46-57), and sharing a sleep surface with another person, 10% (95% CI 4-18). CONCLUSIONS: Pictures on baby diaper packaging in Europe are often inconsistent with SISRs. The prevention of sudden unexpected death in infancy requires action from manufacturers and legislators to stop parents' exposure to misleading images that may lead to dangerous practices.

Alternative CNDOL Fockians for fast and accurate description of molecular exciton properties.

CNDOL is an a priori, approximate Fockian for molecular wave functions. In this study, we employ several modes of singly excited configuration interaction (CIS) to model molecular excitation properties by using four combinations of the one electron operator terms. Those options are compared to the experimental and theoretical data for a carefully selected set of molecules. The resulting excitons are represented by CIS wave functions that encompass all valence electrons in the system for each excited state energy. The Coulomb-exchange term associated to the calculated excitation energies is rationalized to evaluate theoretical exciton binding energies. This property is shown to be useful for discriminating the charge donation ability of molecular and supermolecular systems. Multielectronic 3D maps of exciton formal charges are showcased, demonstrating the applicability of these approximate wave functions for modeling properties of large molecules and clusters at nanoscales. This modeling proves useful in designing molecular photovoltaic devices. Our methodology holds potential applications in systematic evaluations of such systems and the development of fundamental artificial intelligence databases for predicting related properties.

Synthesis and Isolation of Phenol- and Thiol-Derived Epicatechin Adducts Prepared from Avocado Peel Procyanidins Using Centrifugal Partition Chromatography and the Evaluation of Their Antimicrobial and Antioxidant Activity.

Polyphenols from agro-food waste represent a valuable source of bioactive molecules that can be recovered to be used for their functional properties. Another option is to use them as starting material to generate molecules with new and better properties through semi-synthesis. A proanthocyanidin-rich (PACs) extract from avocado peels was used to prepare several semi-synthetic derivatives of epicatechin by acid cleavage in the presence of phenol and thiol nucleophiles. The adducts formed by this reaction were successfully purified using one-step centrifugal partition chromatography (CPC) and identified by chromatographic and spectroscopic methods. The nine derivatives showed a concentration-dependent free radical scavenging activity in the DPPH assay. All compounds were also tested against a panel of pathogenic bacterial strains formed by Listeria monocytogenes (ATCC 7644 and 19115), Staphylococcus aureus (ATCC 9144), Escherichia coli (ATCC 11775 and 25922), and Salmonella enterica (ATCC 13076). In addition, adducts were tested against two no-pathogenic strains, Limosilactobacillus fermentum UCO-979C and Lacticaseibacillus rhamnosus UCO-25A. Overall, thiol-derived adducts displayed antimicrobial properties and, in some specific cases, inhibited biofilm formation, particularly in Listeria monocytogenes (ATCC 7644). Interestingly, phenolic adducts were inactive against all the strains and could not inhibit its biofilm formation. Moreover, depending on the structure, in specific cases, biofilm formation was strongly promoted. These findings contribute to demonstrating that CPC is a powerful tool to isolate new semi-synthetic molecules using avocado peels as starting material for PACc extraction. These compounds represent new lead molecules with antioxidant and antimicrobial activity.

Real-World Experience with Vismodegib on Advanced and Multiple BCCs: Data from the RELIVIS Study.

BACKGROUND: Vismodegib is approved for advanced cases of basal cell carcinomas not amenable to surgery or radiotherapy. Large studies on the use of vismodegib in clinical practice are scarce. OBJECTIVES: The main objective of the study was to analyse the evolution and therapeutic management of relapses and lack of response in patients who had received vismodegib for locally advanced and/or multiple basal cell carcinomas in a real-life multicentre setting. METHODS: This nationwide retrospective study collected data on patients treated with vismodegib in 15 specialized centres. We included patients who first received vismodegib until intolerable toxicity, maximum response, or progressive disease. Exploratory research variables referred to patient and tumour characteristics, vismodegib effectiveness and safety, relapse rate and management, and mortality. A multivariable logistic regression model was used to identify predictors of complete clinical response. RESULTS: 133 patients with advanced BCC were included in the registry. The objective response rate (ORR) was 77.5% and nearly half of the patients (45.9%) achieved complete remission. Long-term information and detailed information of subsequent treatments after a regime of vismodegib was available for 115 patients. Only 34% of the patients in this group were subsequently treated with other therapies or vismodegib rechallenge. Sixty-nine percent of the patients who had shown a complete remission with vismodegib remained free of recurrence while 30.7% relapsed. Almost half of the patients who received additional therapies after the first course of vismodegib achieved complete tumour remission. Three and 2 out of 9 patients who were rechallenged with vismodegib achieved complete and partial responses, respectively, with an ORR of 55.5%. CONCLUSION: Our study confirms efficacy of vismodegib in routine clinical practice. The risk of recurrence after achieving complete response with vismodegib was lower than previous reports. Rechallenge with vismodegib is feasible and most patients responded to re-treatment.

Complicated grief and its relationship with anxiety, depression, and suicidal ideation in older adults in the context of the COVID-19 pandemic in Peru: a cross-sectional analysis.

BACKGROUND: Complicated grief (CG) resulting from poor adaptation to the death of a close person may have been related with the presence of other mental health problems in older adults in Peru during the COVID-19 pandemic. Our study aimed to assess the association between CG and anxiety, depression, and suicidal ideation in older adults in Peru in the context of the COVID-19 pandemic. METHODS: We conducted a cross-sectional analysis using data from the "Socioemotional evaluation form" applied in 2020 to mental health problems in older adults attending the Peruvian Social Security (EsSalud). For our study, we included older adults who reported the death of a close person during the last six months when this assessment was performed. CG, depression, anxiety, and suicidal ideation were initially evaluated using validated questionnaires. The association between CG and the presence of mental health problems was calculated through multivariate analysis, where prevalence ratios (PR) were estimated with 95% confidence intervals (CI). RESULTS: Of the 249 older adults included, 175 (70.3%) were female with a median age of 71 years (interquartile range: 9), and 35 (14.1%) reported the presence of CG. It was found that CG in this population was associated with the presence of anxiety (PR: 1.35, 95% CI: 0.98 to 1.85), depression (PR: 1.44, 95% CI: 1.06 to 1.95), and suicidal ideation (PR: 2.84, 95% CI: 1.06 to 7.59). CONCLUSIONS: CG is related to the presence of mental health problems in older adults in Peru. It is essential to implement measures that facilitate the prevention and proper management of this condition in this population, especially in the context of high population mortality such as the COVID-19 pandemic.

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study.

BACKGROUND: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. METHODS: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. RESULTS: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. CONCLUSIONS: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.

Aggression and burnout in nurses during COVID-19: A cross-sectional study.

Workplace violence against nurses, an ever-present problem in the healthcare workplace, has been increasing with COVID-19 and affects occupational health. This study analyzed the consequences of COVID-19 on violence against nurses, identifying its association with burnout, emphasizing the importance of work-related variables. A total of 1013 actively employed nurses in Spain with a mean age of 34.71 years filled out a computer-assisted web interviewing survey. Aggression as a consequence of their work was reported by 73.44% of the nurses. Those most affected were in primary care, and verbal aggression by patients and their families was the most frequent. Nurses who were attacked scored significantly higher in emotional exhaustion and depersonalization. Furthermore, 83.22% said that COVID-19 was an important factor in the increase in violence toward healthcare workers. Analysis showed that a perceived secure environment was a mediator between the belief that COVID-19 was an influential factor in the increase of violence and the depersonalization dimension of burnout. Increasing perceived security in the work environment among nurses can be effective in promoting well-being, work performance, and commitment to the profession.

Job strain and burnout in Spanish nurses during the COVID-19: resilience as a protective factor in a cross-sectional study.

BACKGROUND: Nurses are frequently exposed to chronic stress in the workplace generating harmful effects such as job strain and burnout. On the contrary, resilience has been shown to be a beneficial variable. The objective of this study was to analyze the relationship between dimensions of the Job Demand Control-Support model, resilience and burnout in nurses, and examine the mediating role of resilience between job strain and burnout. METHODS: A descriptive, cross-sectional study reported in line with the STROBE guidelines. Active nurses were invited to complete an online questionnaire in September, 2020. With snowball sampling, 1013 nurses, with a mean age of 34.71, filled out the Job Content Questionnaire, the Maslach Burnout Inventory and the Resilience Scale. RESULTS: The results showed the existence of four groups of professionals based on job strain. The nurses in the "High Strain" group (high demands and low control) showed higher scores in emotional exhaustion and cynicism, while those in the "Active Job" group scored higher in personal realization and resilience. The findings showed that job strain affects burnout in nurses, and this effect is mediated by resilience. CONCLUSIONS: The findings of this study showed that a high level of resilience could exert a fundamental role in ensuring well-being and proper job performance by nurses. Nursing managers should see to the personable variables or competencies that provide and favor an opportunity for nurses to widen and improve their practice, in pursuance of satisfying and responding better to people's needs and the systems they work for.

Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy.

AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.

Seasonal and Diurnal Variations of BTEX in Ambient Air from a Site Impacted by the Oil Industry in Southeast Mexico.

Atmospheric concentrations of BTEX were measured in an urban site located in the vicinity of an oil storage-distribution facility in Paraiso, Tabasco, Mexico. Samples were collected during two seasons (nortes 2018 and dry 2019). The relative abundance of BTEX mean concentrations was: toluene (5.24 µg m-3) > ethylbenzene (3.92 µg m-3) > m, p-xylene (3.89 µg m-3) > benzene (2.43 µg m-3). BTEX concentrations had a clear diurnal and seasonal pattern, showing higher levels during the dry season due to differences in wind conditions, rainfall patterns and temperature. Statistical analysis showed significant positive correlations among BTEX, indicating that these compounds had common sources. Interspecies ratios revealed that BTEX were originated from sources beyond vehicular traffic and that they were influenced by the transport of local air masses. The assessment of lifetime cancer risk showed that the population in the study area is at possible risk of developing cancer.

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July-December) than in the first one (March-June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials.

BACKGROUND: Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. METHODS: The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232. FINDINGS: The seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3·2-18·0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT. INTERPRETATION: Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression. FUNDING: The 7th EU Framework Programme.

Effectiveness of a combined transcranial direct current stimulation and virtual reality-based intervention on upper limb function in chronic individuals post-stroke with persistent severe hemiparesis: a randomized controlled trial.

BACKGROUND: Functional impairments derived from the non-use of severely affected upper limb after stroke have been proposed to be mitigated by action observation and imagination-based techniques, whose effectiveness is enhanced when combined with transcranial direct current stimulation (tDCS). Preliminary studies in mildly impaired individuals in the acute phase post-stroke show intensified effects when action is facilitated by tDCS and mediated by virtual reality (VR) but the effectiveness in cases of severe impairment and chronic stroke is unknown. This study investigated the effectiveness of a combined tDCS and VR-based intervention in the sensorimotor function of chronic individuals post-stroke with persistent severe hemiparesis compared to conventional physical therapy. METHODS: Twenty-nine participants were randomized into an experimental group, who received 30 minutes of the combined tDCS and VR-based therapy and 30 minutes of conventional physical therapy, or a control group, who exclusively received conventional physical therapy focusing on passive and active assistive range of motion exercises. The sensorimotor function of all participants was assessed before and after 25 one-hour sessions, administered three to five times a week, using the upper extremity subscale of the Fugl-Meyer Assessment, the time and ability subscales of the Wolf Motor Function Test, and the Nottingham Sensory Assessment. RESULTS: A clinically meaningful improvement of the upper limb motor function was consistently revealed in all motor measures after the experimental intervention, but not after conventional physical therapy. Similar limited effects were detected in the sensory function in both groups. CONCLUSION: The combined tDCS and VR-based paradigm provided not only greater but also clinically meaningful improvement in the motor function (and similar sensory effects) in comparison to conventional physical therapy.

Effect of a single-component ceramic conditioner on shear bond strength of precoated brackets to different CAD/CAM materials.

OBJECTIVES: To compare the shear bond strength (SBS) of the CAD/CAM material-bracket interface using three surface treatments: following manufacturers' instructions (MI), Monobond Etch & Prime (MEP) and 9.6% hydrofluoric acid plus silane (9.6% HF), after 24 h of water storage (24 h) and 10,000 cycles of thermocycling (TC). MATERIALS AND METHODS: A total of 126 crowns with four identical buccal surfaces were fabricated using seven different CAD/CAM materials: CEREC Blocs unglazed (CBU), CEREC Blocs glazed (CBG), IPS Empress CAD (EMP), IPS e.max CAD (EMA), VITA SUPRINITY PC (SUP), inCoris TZI (TZI) and VITA ENAMIC (ENA). A total of 504 APC Flash-Free (APC FF)-precoated brackets were bonded applying three surface treatments: (1) MI; (2) MEP and (3) 9.6% HF. SBS was performed after 24 h and TC. Results were analyzed by Kruskal-Wallis and Mann-Whitney U tests (p < 0.05). RESULTS: MEP conditioning yielded lower SBS results compared with MI and 9.6% HF for CBG (24 h and TC) and EMA (TC) materials. EMP conditioning with MEP after 24 h obtained lower SBS values compared with MI; however, after TC, SBS was similar to MI group and higher than with 9.6% HF. After TC for TZI ceramic, MI protocol (sandblasting) obtained higher SBS scores than MEP, but similar than 9.6% HF. Treatment of ENA with MI and MEP produced higher results than 9.6% HF after TC. SBS results were similar for CBU and SUP, regardless of the treatment. CONCLUSIONS: Although each CAD/CAM material requires specific surface treatment to obtain the highest SBS of APC FF brackets, the treatment with MEP is a valid orthodontic alternative for most of the materials tested. TC significantly decreased SBS for most of the materials. CLINICAL RELEVANCE: MEP can be considered a valid and promising product to condition most of the CAD/CAM ceramics evaluated for APC FF bracket bonding purposes, allowing a faster and safer procedure.

Communication Styles Inventory-Brief: Adaptation and validation for Spanish nursing.

Healthcare attention is sometimes considered purely technical, but communication has proven to be closely related to clinical results and patient satisfaction. Therefore, evaluation of communication in the scope of healthcare is a priority. The purpose of this study was to validate and adapt the Spanish version of the Communication Styles Inventory in a sample of nursing professionals. The sample was made up of 2313 nursing professionals selected at random from various medical centres in Spain, and is therefore a sample actively employed at the time data were acquired. We started out from the Communication Style Inventory, a questionnaire for evaluating the predominance of certain individual communication behaviours on six scales (expressiveness, preciseness, verbal aggressiveness, questioningness, emotionality and impression manipulativeness). Confirmatory Factor Analysis of the model proposed showed god fit indices. The reliability of the model shown by the Cronbach's alpha of α = 0.81 was adequate, and so was single-level and aggregate consistency. Finally, in the analysis of variance by type of contract, configural, metric and scalar invariance was acceptable, but not strict invariance. This instrument progresses in measuring non-technical attributes, such as communication styles, in nursing personnel.

Benchmark dose risk analysis with mixed-factor quantal data in environmental risk assessment.

Benchmark analysis is a general risk estimation strategy for identifying the benchmark dose (BMD) past which the risk of exhibiting an adverse environmental response exceeds a fixed, target value of benchmark response (BMR). Estimation of BMD and of its lower confidence limit (BMDL) is well understood for the case of an adverse response to a single stimulus. In many environmental settings, however, one or more additional, secondary, qualitative factor(s) may collude to affect the adverse outcome, such that the risk changes with differential levels of the secondary factor. This paper extends the single-dose BMD paradigm to a mixed-factor setting with a secondary qualitative factor possessing two levels. With focus on quantal-response data and using a generalized linear model with a complementary-log link function, we derive expressions for BMD and BMDL. We study the operating characteristics of six different multiplicity-adjusted approaches to calculate the BMDL, using Monte Carlo evaluations. We illustrate the calculations via an example data set from environmental carcinogenicity testing.

Computing Accurate Probabilistic Estimates of One-D Entropy from Equiprobable Random Samples.

We develop a simple Quantile Spacing (QS) method for accurate probabilistic estimation of one-dimensional entropy from equiprobable random samples, and compare it with the popular Bin-Counting (BC) and Kernel Density (KD) methods. In contrast to BC, which uses equal-width bins with varying probability mass, the QS method uses estimates of the quantiles that divide the support of the data generating probability density function (pdf) into equal-probability-mass intervals. And, whereas BC and KD each require optimal tuning of a hyper-parameter whose value varies with sample size and shape of the pdf, QS only requires specification of the number of quantiles to be used. Results indicate, for the class of distributions tested, that the optimal number of quantiles is a fixed fraction of the sample size (empirically determined to be ~0.25-0.35), and that this value is relatively insensitive to distributional form or sample size. This provides a clear advantage over BC and KD since hyper-parameter tuning is not required. Further, unlike KD, there is no need to select an appropriate kernel-type, and so QS is applicable to pdfs of arbitrary shape, including those with discontinuous slope and/or magnitude. Bootstrapping is used to approximate the sampling variability distribution of the resulting entropy estimate, and is shown to accurately reflect the true uncertainty. For the four distributional forms studied (Gaussian, Log-Normal, Exponential and Bimodal Gaussian Mixture), expected estimation bias is less than 1% and uncertainty is low even for samples of as few as 100 data points; in contrast, for KD the small sample bias can be as large as -10% and for BC as large as -50%. We speculate that estimating quantile locations, rather than bin-probabilities, results in more efficient use of the information in the data to approximate the underlying shape of an unknown data generating pdf.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Coping strategies and stress-induced natural killer cell redistribution in women with eating disorders.

BACKGROUND: Patients with eating disorders (ED) are very sensitive and responsive to psychosocial stress. Stress response includes changes in immune cell distribution and may be modulated by the capability to cope with stressors. Thus, the present study sought to analyze the association between coping strategies and immune response (natural killer [NK] cell redistribution following psychosocial stress) in patients with anorexia nervosa (AN) and bulimia nervosa (BN) and healthy controls (HC). METHOD: Twenty-four AN patients, 29 BN patients, and 58 HC were studied. A multidimensional assessment tool, the COPE Inventory, was used to assess coping strategies. The number of NK cells was quantified in peripheral blood before and after the application of the Trier Social Stress Test (TSST). Potentially mediating variables, such as weight status, severity of eating pathology, depression, anxiety, and impulsivity were controlled. RESULTS: The three groups differed in intensity and direction of cell redistribution: The TSST was followed in BN patients by a significant decrease in the number of NK cells, whereas HC displayed a moderate decrease and AN a clear increase. Specific correlations between coping strategies and NK cell mobilization were found, especially in BN patients (positive for "planning" and negative for "substance abuse"). CONCLUSION: Recognition and subsequent modification of the dysfunctional coping strategies used by patients with ED could contribute to improving their immune status, strengthening their resilience and increasing their ability to overcome the disease.

ANTECEDENTES: Los pacientes con trastornos de la conducta alimentaria (TCA) son muy sensibles y respondedores ante el estrés psicosocial. La respuesta al estrés incluye cambios en la distribución de las células inmunes y parece estar modulada por la capacidad de afrontamiento del individuo. En este contexto, el objetivo del presente estudio fue analizar la asociación entre estrategias de afrontamiento y redistribución tras el estrés de las células agresoras naturales (natural killer, NK) en pacientes de sexo femenino con anorexia nervosa (AN) y bulimia nervosa (BN), y controles sanos (CS). MÉTODO: Treinta y cuatro pacientes con AN, 29 pacientes con BN y 58 CS fueron estudiados. Para evaluar las estrategias de afrontamiento se utilizó un instrumento multidimensional, el Inventario COPE. El número de células NK en sangre periférica fue cuantificado antes y después de la aplicación del Trier Social Stress Test (TSST). Las posibles variables mediadoras, como el estado ponderal, la gravedad de la patología alimentaria, depresión, ansiedad e impulsividad fueron control. RESULTADOS: Los tres grupos difirieron en la intensidad y la dirección de la redistribución de células NK: el TSST fue seguido de una notable reducción en el número de células NK en las pacientes con BN, de una disminución moderada en las CS y de un claro incremento en las pacientes con AN. Se encontraron correlaciones específicas entre estrategias de afrontamiento y movilización de células NK, especialmente en las pacientes con BN (positiva para "planificación" y negativa para "abuso de sustancias"). CONCLUSIÓN: El reconocimiento y la modificación consiguiente de las estrategias de afrontamiento disfuncionales utilizadas por las pacientes con TCA pueden contribuir a mejorar su estado inmunológico, incrementando su resistencia y su capacidad para superar la enfermedad.

The mediating role of cognitive and affective empathy in the relationship of mindfulness with engagement in nursing.

BACKGROUND: The work of health professionals is characterized by a high demand for psychological and emotional resources and high levels of stress. Therefore, the promotion of commitment and job well-being through strategies such as increased mindfulness, is important among nursing workers. Although mindfulness has shown positive effects in the health field, few studies have explored the mechanisms and processes underlying these results. We investigated the mediating role of empathy (cognitive/affective) in the effect of mindfulness on the dimensions of engagement in nursing professionals. METHODS: Sample was comprised of 1268 Spanish nurses between 22 and 62 years old, that completed the Utrecht Labor Engagement Scale and the adapted versions of Mindful Attention Awareness Scale and Basic Empathy Scale. The relationship between variables to be included in the regression analyses, bivariate correlations were carried out, and the descriptive statistics of these variables were also found. To estimate the mediation model was used, in this case for multiple mediation effects. RESULTS: Mindfulness is found to affect the Vigor and Dedication factors of engagement through cognitive empathy. While for the Absorption factor, the affective component of empathy also exerts a mediating role, although weaker than cognitive empathy. Cognitive empathy, as an individual factor, was shown to have a mediating effect between mindfulness and the factors of engagement in healthcare workers. CONCLUSIONS: The level of mindfulness influences engagement of nursing professionals positively, and this result is mediated mainly by cognitive empathy. Both mindfulness and empathy are modifiable individual factors, so their intervention by designing and implementing specific programs, can increase the commitment and wellbeing of professionals generating benefits to workers and to their patients.