Synthesis of large-pore zeolites from chiral structure-directing agents with two l-prolinol units

In this work, we perform an in-depth experimental and computational study about the structure-directing effect of two new chiral organic quaternary ammonium dications bearing two N-methyl-prolinol units linked by a xylene spacer in para or meta relative orientation, displaying four enantiopure stereogenic centers in (S) configuration. Synthesis results show that the para-xylene derivative is an efficient structure-directing agent, promoting the crystallization of ZSM-12 (in pure-silica composition), beta zeolite (as pure-silica, or in the presence of Al or Ge), and a mixture of polymorphs C, A and B of zeolite beta (in the presence of Ge). In contrast, the meta-xylene derivative showed a much poorer structure-directing activity, yielding only amorphous materials unless Ge is present in the gel, where beta and polymorph C (together with A and B) zeolites crystallized. Molecular simulations showed that the para-xylene dication displays a cylindrical shape suitable for confining in zeolite pores, while the meta-xylene derivative has an angular shape that shifts from the typical dimensions required for 12MR zeolite channels. Despite enantio-purity of the para-xylene dication with (S, S, S, S) configuration, no enrichment in polymorph A of the zeolite beta samples obtained was observed by Transmission Electron Microscopy. With the aid of molecular simulations, the failure in transferring chirality to the zeolite is explained by the loose fit of this SDA in the large-pores of zeolite beta, and a lack of close geometrical fit with the chiral element of polymorph A, as evidenced by the very similar interaction of the cation with the two enantiomorphic space groups of polymorph A. Nevertheless, the molecular-level knowledge gained in this work can provide insights for the future design of more efficient SDAs towards the synthesis of chiral zeolites

Impact of coronavirus syndromes on physical and mental health of health care workers: Systematic review and meta-analysis

Background: Health care workers (HCW) are at high risk of developing physical/mental health outcomes related to coronavirus syndromes. Nature and frequency of these outcomes are undetermined. Methods: PRISMA/MOOSE-compliant (PROSPERO-CRD42020180205) systematic review of Web of Science/grey literature until 15th April 2020, to identify studies reporting physical/mental health outcomes in HCW infected/exposed to Severe Acute Respiratory Syndrome -SARS-, Middle East Respiratory Syndrome -MERS-, Novel coronavirus -COVID-19-. Proportion random effect meta-analyses, I2 statistic, quality assessment and sensitivity analysis. Results: 115 articles were included (n=60,458 HCW, age 36.1±7.1, 77.1% female). Physical health outcomes: 75.9% HCW infected by SARS/MERS/COVID-19 reported fever (95%CI=65.9–83.7%, k=12, n=949), 47.9% cough (95%CI=39.2–56.8%, k=14, n=970), 43.6% myalgias (95%CI=31.9–56.0%, k=13, n=898), 42.3% chills (95%CI=20.2–67.9%, k=7, n=716), 41.2% fatigue (95%CI=18.2–68.8%, k=6, n=386), 34.6% headaches (95%CI=23.1–48.2%, k=11, n=893), 31.2% dyspnoea (95%CI=23.2–40.5%, k=12, n=1003), 25.3% sore throat (95%CI=18.8–33.2%, k=8, n=747), 22.2% nausea/vomiting (95%CI=14.9–31.8%, k=6, n=662), 18.8% diarrhoea (95%CI=11.9–28.4%, k=9, n=824). Mental health outcomes: 62.5% HCW exposed to SARS/MERS/COVID-19 reported general health concerns (95%CI=57.0–67,8%, k=2, n=2254), 43.7% fear (95%CI=33.9–54.0%, k=4, n=584), 37.9% insomnia (95%CI=30.9–45.5%, k=6, n=5067), 37.8% psychological distress (95%CI=28.4–48.2%, k=15, n=24,346), 34.4% burnout (95%CI=19.3–53.5%, k=3, n=1337), 29.0% anxiety features (95%CI=14.2–50.3%, k=6, n=9191), 26.3% depressive symptoms (95%CI=12.5–47.1%, k=8, n=9893), 20.7% post-traumatic stress disorder features (95%CI=13.2–31%, k=11, n=3826), 16.1% somatisation (95%CI=0.2–96.0%, k=2, n=2184), 14.0% stigmatisation feelings (95%CI=6.4–28.1%, k=2, n=411). Limitations: Limited amount of evidence for some outcomes and suboptimal design in several studies included. Conclusions: SARS/MERS/COVID-19 have a substantial impact on the physical and mental health of HCW, which should become a priority for public health strategies

Multiscale entropy analysis of unattended oximetric recordings to assist in the screening of paediatric sleep apnoea at home

Producción CientíficaUntreated paediatric obstructive sleep apnoea syndrome (OSAS) can severely affect the development and quality of life of children. In-hospital polysomnography (PSG) is the gold standard for a definitive diagnosis though it is relatively unavailable and particularly intrusive. Nocturnal portable oximetry has emerged as a reliable technique for OSAS screening. Nevertheless, additional evidences are demanded. Our study is aimed at assessing the usefulness of multiscale entropy (MSE) to characterise oximetric recordings. We hypothesise that MSE could provide relevant information of blood oxygen saturation (SpO2) dynamics in the detection of childhood OSAS. In order to achieve this goal, a dataset composed of unattended SpO2 recordings from 50 children showing clinical suspicion of OSAS was analysed. SpO2 was parameterised by means of MSE and conventional oximetric indices. An optimum feature subset composed of five MSE-derived features and four conventional clinical indices were obtained using automated bidirectional stepwise feature selection. Logistic regression (LR) was used for classification. Our optimum LR model reached 83.5% accuracy (84.5% sensitivity and 83.0% specificity). Our results suggest that MSE provides relevant information from oximetry that is complementary to conventional approaches. Therefore, MSE may be useful to improve the diagnostic ability of unattended oximetry as a simplified screening test for childhood OSAS.Sociedad Española de Neumología y Cirugía Torácica (SEPAR) project 153/2015Junta de Castilla y León (Consejería de Educación) y el Fondo Europeo de Desarrollo Regional (FEDER), projects (RTC-2015-3446-1) y (TEC2014-53196-R)Ministerio de Economía y Competitividad (MINECO) y FEDER, y el proyecto POCTEP 0378_AD_EEGWA_2_P de la Comisión Europea. L.National Institutes of Health (NIH) grant 1R01HL130984-01Ministerio de Asuntos Económicos y Transformación Digital, grant IJCI-2014-2266

Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN)

BACKGROUND: Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes. METHODS: Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low:  20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV). RESULTS: A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (− 2.74 [− 3.28; − 2.21] and − 0.12 [− 0.15; − 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements. CONCLUSIONS: Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registration NCT04143503, registered on October 25, 2019. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-022-03997-z

Symbolic dynamics to enhance diagnostic ability of portable oximetry from the Phone Oximeter in the detection of paediatric sleep apnoea

Objective: This study is aimed at assessing symbolic dynamics as a reliable technique to characterize complex fluctuations of portable oximetry in the context of automated detection of childhood obstructive sleep apnoea-hypopnoea syndrome (OSAHS). Approach: Nocturnal oximetry signals from 142 children with suspected OSAHS were acquired using the Phone Oximeter: a portable device that integrates a pulse oximeter with a smartphone. An apnoea-hypopnoea index (AHI) ⩾ 5 events h−1 from simultaneous in-lab polysomnography was used to confirm moderate-to-severe childhood OSAHS. Symbolic dynamics was used to parameterise non-linear changes in the overnight oximetry profile. Conventional indices, anthropometric measures, and time-domain linear statistics were also considered. Forward stepwise logistic regression was used to obtain an optimum feature subset. Logistic regression (LR) was used to identify children with moderate-to-severe OSAHS. Main results: The histogram of 3-symbol words from symbolic dynamics showed significant differences (p < 0.01) between children with AHI < 5 events h−1 and moderate-to-severe patients (AHI ⩾ 5 events h−1). Words representing increasing oximetry values after apnoeic events (re-saturations) showed relevant diagnostic information. Regarding the performance of individual characterization approaches, the LR model composed of features from symbolic dynamics alone reached a maximum performance of 78.4% accuracy (65.2% sensitivity; 86.8% specificity) and 0.83 area under the ROC curve (AUC). The classification performance improved combining all features. The optimum model from feature selection achieved 83.3% accuracy (73.5% sensitivity; 89.5% specificity) and 0.89 AUC, significantly (p <0.01) outperforming the other models. Significance: Symbolic dynamics provides complementary information to conventional oximetry analysis enabling reliable detection of moderate-to-severe paediatric OSAHS from portable oximetry

Time Course and Pattern of Metastasis of Cutaneous Melanoma Differ between Men and Women

Background: This study identified sex differences in progression of cutaneous melanoma. Methodology/Principal Findings: Of 7,338 patients who were diagnosed as an invasive primary CM without clinically detectable metastases from 1976 to 2008 at the University of Tuebingen in Germany, 1,078 developed subsequent metastases during follow up. The metastatic pathways were defined in these patients and analyzed using the Kaplan-Meier method. Multivariate survival analysis was performed using Cox modeling. In 18.7 % of men and 29.2 % of women (P,0.001) the first metastasis following diagnosis of primary tumor was locoregional as satellite/in-transit metastasis. The majority of men (54.0%) and women (47.6%, P = 0.035) exhibited direct regional lymph node metastasis. Direct distant metastasis from the stage of the primary tumor was observed in 27.3 % of men and 23.2 % of women (P = 0.13). Site of first metastasis was the most important prognostic factor of survival after recurrence in multivariate analysis (HR:1.3; 95 % CI: 1.0–1.6 for metastasis to the regional lymph nodes vs. satellite/in-transit recurrence, and HR:5.5; 95 % CI: 4.2–7.1 for distant metastasis vs. satellite/ in-transit recurrence, P,0.001). Median time to distant metastasis was 40.5 months (IQR, 58.75) in women and 33 months (IQR, 44.25) in men (P = 0.002). Five-year survival after distant recurrence probability was 5.2 % (95 % CI: 1.4–2.5) for men compared with 15.3 % (95 % CI: 11.1–19.5; P = 0.008) for women. Conclusions/Significance: Both, the pattern of metastatic spread with more locoregional metastasis in women, and th