Donors, acceptors, and a bit of aromatics: electronic interactions of molecular adsorbates on hBN and MoS2 monolayers.

The design of low-dimensional organic-inorganic interfaces for the next generation of opto-electronic applications requires in-depth understanding of the microscopic mechanisms ruling electronic interactions in these systems. In this work, we present a first-principles study based on density-functional theory inspecting the structural, energetic, and electronic properties of five molecular donors and acceptors adsorbed on freestanding hexagonal boron nitride (hBN) and molybdenum disulfide (MoS2) monolayers. All considered interfaces are stable, due to the crucial contribution of dispersion interactions, which are maximized by the overall flat arrangement of the physisorbed molecules on both substrates. The level alignment of the hybrid systems depends on the characteristics of the constituents. On hBN, both type-I and type-II interfaces may form, depending on the relative energies of the frontier orbitals with respect to the vacuum level. On the other hand, all MoS2-based hybrid systems exhibit a type-II level alignment, with the molecular frontier orbitals positioned across the energy gap of the semiconductor. The electronic structure of the hybrid materials is further determined by the formation of interfacial dipole moments and by the wave-function hybridization between the organic and inorganic constituents. These results provide important indications for the design of novel low-dimensional hybrid materials with suitable characteristics for opto-electronics.

Anticoagulation Monitoring Under ECMO Support: A Comparative Study Between the Activated Coagulation Time and the Anti-Xa Activity Assay.

PURPOSE: Extra Corporeal Membrane Oxygenation (ECMO) is used in cases of severe respiratory and/or circulatory failure over periods of several days to several weeks. Its circuitry requires a closely monitored anticoagulation therapy that is empirically supported by activated clotting time (ACT)-a method often associated with large inter- and intraindividual variability. We aimed to compare the measurement of heparin activity with ACT and the direct measurement of the heparin activity (anti-Xa) in a large ECMO population. METHODS: All patients treated by venoarterial or venovenous ECMO in our intensive care unit between January 2014 and December 2015 were prospectively included. A concomitant measurement of the anti-Xa activity and ACT was performed on the same sample collected twice a day (morning-evening) for unfractionated heparin adaptation with an ACT target range of 180 to 220 seconds. RESULTS: One hundred and nine patients (men 69.7%, median age 54 years) treated with ECMO (70.6% venoarterial) were included. Spearman analysis found no correlation between anti-Xa and ACT (ρ < 0.4) from day 1 and worsened over time. Kappa analysis showed no agreement between the respective target ranges of ACT and anti-Xa. CONCLUSIONS: We demonstrate that concomitant measurement of ACT and anti-Xa activity is irrelevant in ECMO patients. Since ACT is poorly correlated with heparin dosage, anti-Xa activity appears to be a more suitable assay for anticoagulation monitoring.

The factor VIII:C/VWF:Ag ratio as a useful tool to predict relapse in patients with acquired haemophilia A: A retrospective cohort study.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of autoantibodies against coagulation factor VIII (FVIII). The mortality rate remains high. International recommendations define complete remission as undetectable inhibitor (<0.6 Bethesda Units [BU]) and normal FVIII activity (FVIII:C) that persists after immunosuppressive therapy stopped. For patients achieving remission, the risk of relapse reaches 20%. The risk factors for this relapse are not well known. AIM: In this study, we examined the accuracy of the FVIII/W ratio (FVIII:C/von Willebrand Factor Antigen (VWF:Ag) ratio) to predict relapse in 64 consecutive patients with AHA. RESULTS: In this cohort, all patients had a very low FVIII/W ratio at the time of diagnosis, and this value progressively increased in the first weeks of immunosuppressive treatment. In our study, 9/55 (14%) did not achieve complete remission. Twenty-seven patients were followed long enough (more than a year) to show that in the 22 patients who did not relapse, the FVIII/W ratio remained durably normalized. By contrast, in the five patients who relapsed during follow-up, we noted either no normalization of the FVIII/W ratio, or a secondary decrease to an abnormal value of <0.7 after initial normalization. In all patients who relapsed, the ratio was the first abnormal biological result to be observed, always preceding changes in the activated partial thromboplastin time (aPTT), FVIII:C and anti-FVIII reappearance. CONCLUSION: These data suggest that the FVIII/W ratio could be considered a sensitive biological marker to predict recovery and/or relapse in AHA.

Pediatric patients with lysosomal acid lipase deficiency.

Lysosomal acid lipase (LAL) deficiency is a rare, autosomal recessive disease caused by mutations in the LIPA gene, which produces cholesteryl ester and triglyceride accumulation predominantly in hepatocytes, adrenal glands, and gastrointestinal tract. We describe two new cases occurring in siblings, aged 5 and 7 years, who presented with hepatomegaly, dyslipidemia, and abnormal liver function. Percutaneous liver biopsy revealed portal inflammation, hypertrophic Kupffer cells with a foamy appearance and microvesicular steatosis with fibrosis. Immunostaining for lysosomal markers, cathepsin D and LAMP1 reflected the lysosomal nature of the lipid vacuoles. After enzymatic confirmation, enzyme replacement therapy was initiated for both siblings. Follow-up transaminase levels and lipid profiles showed a notable decrease in AST and ALT and a slight increase in HDL cholesterol. It is crucial to increase awareness of this rare condition among clinicians and pathologists. The expression of lysosomal markers around the lipid vacuoles might help diagnose LAL deficiency in pediatric patients.

Genetics, Morphometrics and Health Characterization of Green Turtle Foraging Grounds in Mainland and Insular Chile.

Two divergent genetic lineages have been described for the endangered green turtle in the Pacific Ocean, occurring sympatrically in some foraging grounds. Chile has seven known green turtle foraging grounds, hosting mainly juveniles of different lineages. Unfortunately, anthropic factors have led to the decline or disappearance of most foraging aggregations. We investigated age-class/sex structure, morphological variation, genetic diversity and structure, and health status of turtles from two mainland (Bahia Salado and Playa Chinchorro) and one insular (Easter Island) Chilean foraging grounds. Bahia Salado is composed of juveniles, and with Playa Chinchorro, exclusively harbors individuals of the north-central/eastern Pacific lineage, with Galapagos as the major genetic contributor. Conversely, Easter Island hosts juveniles and adults from both the eastern Pacific and French Polynesia. Morphological variation was found between lineages and foraging grounds, suggesting an underlying genetic component but also an environmental influence. Turtles from Easter Island, unlike Bahia Salado, exhibited injuries/alterations probably related to anthropic threats. Our findings point to establishing legal protection for mainland Chile's foraging grounds, and to ensure that the administrative plan for Easter Island's marine protected area maintains ecosystem health, turtle population viability, and related cultural and touristic activities.

Immune-related adverse events of biological immunotherapies used in COVID-19.

The use of biological immunotherapeutic drugs is one of the options currently being evaluated and employed to manage COVID-19, specifically monoclonal antibodies, which have shown benefit by regulating the excessive immune response seen in patients with severe infection, known as a cytokine storm. Tocilizumab has received particular importance for this clinical application, as has sarilumab. Both drugs share a substantial similarity in terms of pharmacodynamics, being inhibitors of the interleukin six receptor (IL-6Rα). Furthermore, sotrovimab, a neutralizing anti-SARS CoV-2 antibody, has gained the attention of the scientific community since it has recently been authorized under certain circumstances, positioning itself as a new therapeutic alternative in development. However, despite their clinical benefit, biological immunotherapies have the potential to generate life-threatening immune-related adverse events. Therefore it is essential to review their incidence, mechanism, and risk factors. This review aims to provide a comprehensive understanding of the safety of the biological immunotherapeutic drugs currently recommended for the treatment of COVID-19, provide a review of the known immune-mediated adverse events and explore the potential immune-related mechanisms of other adverse reactions.

False Contraindications for Vaccinations Result in Sub-Optimal Vaccination Coverage in Quito, Ecuador: A Cross-Sectional Study.

Vaccination coverage in Ecuador has decreased since 2013, falling short of the World Health Organization's vaccination goal. There are several causes for this deficiency in coverage, one of these are lost vaccination opportunities, which are caused when a patient without contraindications postpones, or for other reasons fails to receive a recommended immunization. The objective of this study was to determine the state of knowledge regarding vaccination contraindications among the Metropolitan District of Quito health personnel to assess missed vaccination opportunities. Through this cross-sectional descriptive study, health personnel were surveyed online and asked 18 clinical scenarios which were created to evaluate their knowledge of the true contraindications of vaccination, and measure missed opportunities. A total of 273 surveys were collected; 74% belonged to the public health system, and the rest represented by private practitioners. Of those surveyed, 98.2% of health personnel had improperly denied vaccination at least once. We specifically found vaccinations were incorrectly denied more frequently in cases where the hypothetical patient presented mild or moderate fever cases. The use of corticosteroids, autoimmune diseases, and egg allergy were also incorrectly denied (89%, 71.4%, 72.9%, and 58.6%, respectively). Among the health personnel surveyed, there is an apparent lack of knowledge of the true contraindications of vaccination and differences in knowledge about contraindications according to personnel in charge of administering immunization to children. Our preliminary results suggest that lack of education related to side effects could be biasing medical professionals' decisions, causing them to unnecessarily delay or deny vaccinations, which likely contributes to explaining low overall vaccination coverage in Quito, the capital city of Ecuador.

Platelet function defects and sertraline-induced bleeding: a case report.

A 71-year-old man is admitted for nose bleeds recurring for several days. His medical background shows in particular major depression for which he has been receiving sertraline for several years. The workup shows anemia, and no anomalies on head and neck CT angiography. However, further explorations suggest an acquired thrombopathy that could have contributed to the bleeding. During sertraline exposure, platelet functional exploration and platelet secretion were abnormal. Sertraline is often used as first-line treatment of depression. Pharmacological data and spontaneous notifications suggest increased potential risk with sertraline. It appears necessary to pay attention to bleeding with sertraline use.

Stopping or maintaining oral anticoagulation in patients undergoing photoselective vaporization of the prostate (SOAP) surgery for benign prostate obstruction: study protocol for a multicentre randomized controlled trial.

BACKGROUND: Lower urinary tract symptoms related to benign prostatic obstruction (BPO) are frequent in men aged > 50 years. Based on the use of innovative medical devices, a number of transurethral ablative techniques have recently been developed for the surgical treatment of BPO. In recent years, GreenLight photoselective vaporization of the prostate (PVP) has been considered as a non-inferior alternative to transurethral resection of the prostate. The GreenLight PVP is usually considered as an interesting surgical option for patients treated via oral anticoagulants (OACs) with regard to its haemostatic properties. The aim of this study was to assess the impact of maintaining OAC treatment in patients undergoing PVP. METHODS: This study is a multicentre, open-label, randomized controlled trial (RCT) designed to show the non-inferiority of PVP surgery in patients with BPO treated with OACs. This study is designed to enrol 386 OAC-treated patients (treated with vitamin K antagonists and direct oral anticoagulants) who are undergoing PVP for BPO. Patients will be randomized (1:1) to either maintain or stop OAC treatment during the perioperative course. The intervention group will maintain OAC treatment until the day before surgery and resume OAC treatment the day after surgery, whereas the control group will stop OAC treatment (with or without low-molecular-weight heparin bridging therapy) according to the anaesthesia guidelines. The primary outcome of interest to be assessed is the 30-day complications rate according to the Clavien-Dindo classification. The secondary endpoint will examine the 30-day rate of haemorrhagic and thrombotic events. This study will provide 80% power to show non-inferiority, defined as not worse than a 10% (non-inferiority margin) inferior change in the proportion of patients with good outcomes (Clavien-Dindo score < 2), using two-tailed 95% confidence intervals. DISCUSSION: This first multicentre RCT in the field is underway to evaluate the safety and efficacy of PVP in patients with ongoing OAC therapy. The study results could influence the perioperative management of OACs in BPO surgery with a high level of evidence. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03297281 . Registered on 29 September 2017.

Terapia miofuncional en síndrome de apnea obstructiva del sueño (AOS): revisión de la literatura / Myofunctional therapy in obstructive sleep apnea syndrome (OSA): a literature review

La terapia miofuncional orofacial (TMO) ha tenido un creciente desarrollo durante la última década, presentándose como una opción terapéutica en pacientes con AOS. Sin embargo, la evidencia es limitada y en Chile no hay mucho conocimiento al respecto. Se desarrolló una revisión sistemática en PubMed, MEDLINE, Embase, Web of Science, Lilacs y Scielo, que incluyó estudios primarios publicados en los últimos 10 años en idioma inglés, español o portugués y que utilizaran la TMO en pacientes adultos con AOS. Se excluyeron estudios que combinaran otras estrategias, con alteraciones miofuncionales secundarias a patologías concomitantes y con otro tipo de trastorno del sueño. La revisión consideró 9 artículos en su análisis; los resultados mostraron beneficios significativos a favor de la TMO en relación a disminución del índice de apnea-hipopnea, mejor calidad del sueño, nivel de somnolencia de Epworth, menor intensidad y frecuencia de los ronquidos, menor circunferencia del cuello, entre otros. Se concluye que la TMO genera beneficios en los pacientes con AOS, siendo una opción no invasiva y accesible.

Orofacial myofunctional therapy (OMT) has had a growing development during the last decade, presenting itself as a therapeutic option in patients with OSA. However, the evidence is limited and in Chile there is not much knowledge about it. A systematic review was developed in PubMed, MEDLINE, Embase, Web of Science, Lilacs and Scielo, which included primary studies published in the last 10 years in English, Spanish or Portuguese that used OMT in adult patients with OSA. Studies that combined other strategies, with myofunctional alterations secondary to concomitant pathologies and with another type of sleep disorder were excluded. The review considered 9 articles in its analysis; The results showed significant benefits in favor of OMT in relation to a decrease in the apnea-hypopnea index, better sleep quality, Epworth sleepiness level, less intensity and frequency of snoring, less neck circumference, among others. It is concluded that OMT generates benefits in patients with OSA, being a non-invasive and accessible option.

Comparison of three activated protein C resistance tests in the risk assessment of venous thrombosis in non-carriers of the factor V Leiden mutation.

Activated protein C resistance (APCR), measured using the original assay described by Dahlbäck, is a risk factor for venous thrombosis independent of the factor V Leiden (FVL) mutation. This assay is based on the activated partial thromboplastin time (APTT) after plasma exposure to activated protein C (APC). As this assay was sensitive to numerous interferences, new assays have been developed for FVL screening. The objectives of the study were to investigate the association of second generation assays for APCR with venous thrombosis in FVL non-carriers. One hundred ninety-seven subjects with a history of venous thrombosis and 211 controls were explored using 3 APCR assays, the original APTT-based assay (test A), an APTT-based assay with factor V depleted plasma pre-dilution (test B) and a direct factor X activation-based assay with the same pre-dilution (test C). We found that subjects with results in the lowest quartile of the APTT-based assays are at increased risk, compared to those in the highest quartile (test A Odds Ratio = 6.39; 95% CI 3.23-12.63; test B OR = 2.72; 95% CI 1.50-4.94). There was no significant risk increase associated with test C results. After adjusting for FVIII levels, the ORs of tests A and B were similar (test A OR = 3.22; 95% CI 1.47-7.08; test B OR = 3.10; 95% CI 1.54-6.21). In conclusion, APTT-based assays, but not direct factor X activation-based assays, effectively detect the risk for venous thrombosis independent of FVL. Pre-dilution in factor V depleted plasma is an effective way to directly assess the risk independent of FVIII levels.

Assessment of proximal isovelocity surface area (PISA) shape using three-dimensional echocardiography in a paediatric population with mitral regurgitation or ventricular shunt.

BACKGROUND: The proximal isovelocity surface area (PISA) method is validated to quantify mitral regurgitation (MR) and ventricular shunt (VS). However, the two-dimensional echocardiography (2DE) PISA method assumes a hemispherical distribution of velocity factors proximal to the MR or VS orifice. AIM: To assess the PISA shape by three-dimensional echocardiography (3DE) in a paediatric population with MR or VS. According to the true PISA shape, we suggest different models to calculate the MR or VS volume by the 3DE PISA method. METHODS: Thirty-one paediatric patients (aged 1month to 20years, median 69months) were included: 17 had MR and 14 had VS. The orifice area and volume of MR and VS were evaluated by 2DE. 3DE acquired the entire PISA volume at orifice level. The PISA shape was estimated according to three diameters as being hemispherical, prolate hemispheroid, oblate hemispheroid and hemiellipsoid. RESULTS: Data from 28patients were analysed. The PISA shape was variable: hemispherical, 11%; prolate hemispheroid, 43%; oblate hemispheroid, 32%; hemiellipsoid, 14%. Oblate hemispheroids occurred more frequently in the MR group (47%), whereas prolate hemispheroids occurred more frequently in the VS group (62%); hemispheres were scarce in both groups (10%). The mean MR or VS orifices and volumes measured by 2DE and 3DE were significantly different (0.123cm(2) versus 0.094cm(2) and 13.2mL versus 10.1mL, respectively; p=0.019). CONCLUSIONS: 3DE describes the true surface of the PISA shape. In a paediatric population with MR or VS, the PISA is rarely hemispherical but is more often prolate or oblate hemispheroid.

Hernia inguinal del niño vs hernia inguinal del adulto / inguinal Hernia of the young inguinal versus hernia adult

Presenta un estudio prospectivo comparativo de 200 casos de hernias inguinales realizado en niños y en adultos, a partir de enero de 1992 hasta diciembre de 1997 en la Clínica de Especialidades Médicas Paucarbamba de la ciudad de Cuenca y el Policlínico Santa Isabel de dicho cnatón, donde se demuestra las diferencias anatómicas, técnicas quirúrgicas, evolución, costos e integración a sus actividades diarias...