The role of childhood cumulative trauma in the risk of lifetime PTSD: An epidemiological study.

Cumulative trauma is usually devastating and can lead to severe psychological consequences, including posttraumatic stress disorder (PTSD). Exposure to various types of traumas, particularly during childhood, can be even more deleterious than the sheer number of events experienced. This epidemiological study is the first to investigate the impact of discrete childhood traumatic exposure on the risk of developing lifetime PTSD in a representative sample of the general population of the two biggest Brazilian cities. Participants were aged between 15 and 75 years old, living in São Paulo and Rio de Janeiro, Brazil, who had experienced traumatic events (N = 3,231). The PTSD diagnosis was assessed using the DSM-IV criteria through the version 2.1 of Composite International Diagnostic Interview. To operationalize childhood cumulative trauma, we considered the sum of 15 different childhood trauma categories that occurred before PTSD onset. The final multivariate logistic regression model indicated a strong relationship between the number of discrete types of childhood traumas and the likelihood of the lifetime PTSD development. The lifetime PTSD risk increased 28 % with each different type of childhood trauma when adjusted by confounds. Our study strengthens the evidence associating childhood cumulative trauma to increased lifetime PTSD risk.

How appropriate is treating patients diagnosed with advanced esophageal cancer with anticancer drugs? A multicenter retrospective cohort Spanish study.

AIM: To assess the appropriateness of systemic oncological treatments (SOT) provided to patients diagnosed with advanced esophageal cancer (EC) across a group of participating hospitals. METHODS: Multicenter, retrospective cohort study in five Spanish hospitals including newly confirmed advanced EC cases between July 1, 2014, and June 30, 2016, with a 5-year follow-up. RESULTS: We identified 157 patients fulfilling the inclusion criteria (median age: 65 years, 85.9% males). Most patients, 125 (79.6%) were treated at least with one active treatment, and 33% received two or more lines of SOT. The 1-, 2- and 5-year overall survival rates were 30.3% [95%CI: 23.8, 38.7], 14.0% [95%CI: 9.3, 21.0], and 7.1% [95% CI: 3.8, 13.1] respectively, and the median survival time 8 months (95% CI: 6, 19) for stages IIIb IIIc and 7 months (95% CI: 5, 9) for stage IV. Clinical stage, receiving more than one line of SOT, and treatment with radiotherapy accelerated the time to death (0.4, 0.9-, and 0.8-times shorter survival respectively, p < 0.05). Better performance status (ECOG < 2) extended survival time by 2.2 times (p = 0.04). Age < 65 years (OR 9.4, 95% CI 3.2, 31.4, p < 0.001), and being treated in one particular hospital (OR 0.2, 95% CI 0.0, 0.8, p < 0.01) were associated with the administration of two or more lines of SOT. Altogether, 18.9% and 9.0% of patients received chemotherapy in the last four and two weeks of life, respectively. Moreover, 2.5% of patients were prescribed a new line of chemotherapy during the last month of life. The proportion of all patients who did not have access to palliative care reached 29.3%, and among those who had access to it, 34.2% initiated it in the last month of life. CONCLUSION: A high proportion of advanced EC patients receive many treatments not based on sound evidence and they do not benefit enough from palliative care services. The most accepted appropriateness indicators point out that some of the analyzed patients could have been overtreated. This study provides important insights into the quality of care provided to advanced EC, and furthermore, for giving valuable insight and opportunities for improvement.

Prevalencia de caídas en pacientes ingresados en un hospital universitario / Prevalence of falls in patients admitted to a University Hospital

Objetivo: analizar la prevalencia de caídas de los pacientes hos­pitalizados en un hospital universitario, así como los factores asociados con la asistencia sanitaria (motivos de las caídas, especialidad más prevalente, turno más frecuente, si estaban solos o acompañados, etc.) en los pacientes que se cayeron y las posibles consecuencias de las caídas. Métodos: estudio transversal. Se incluyeron a todos los pacientes adultos ingresados en 20 unidades de hospitalización del Hospital Universitario de Burgos, que habían sufrido una caída en 2019 y estaban incluidos en el registro de caídas del programa GACELA Care®. El formulario consta de 28 campos de en­trada de datos, que aportan información relevante sobre la caída. Se llevó a cabo análisis descriptivo y comparativo, usando los test estadísticos correspondientes. Resultados: se registraron 244 caídas (0,9%). La edad media fue 73,3 años. El 54,4% tenía edad igual o mayor a 75 años. El 57,8% era del sexo masculino. En Medicina Interna (29,1%) y Psiquiatría (11,1%) se registró el mayor porcentaje de caídas. El 44,2% se produjo en turno de noche, en pacientes que estaban solos (71,7%), sin protecciones (70,5%); y deambulando (36,1%). El motivo principal fue la inestabilidad motora (48,4%). El 62,7% de los pacientes resultó ileso. La especialidad y el turno de trabajo se asociaron significativamente con las caídas. Conclusiones: la prevalencia de caídas en el hospital fue baja. Los factores que se relacionaron con mayor porcentaje de caídas fueron ser mayor de 75 años, sexo masculino, estar ingresado en unidades de especialidad médica y turno de noche. Las caídas ocurrieron habitualmente cuando el paciente estaba solo, sin protección, al levantarse y caminar. La mayoría de los pacientes no presentó lesiones.(AU)

Objective: to analyse the prevalence of falls in patients admitted to a University Hospital, as well as to identify the characteristics of those patients who experienced falls, the factors associated with patient care (reasons for falls, the most prevalent specialty, the most frequent shift, whether they were alone or accompanied, etc.) among patients who fell down, and the potential consequences of said falls. Methods: a cross-sectional study, including all adult patients admitted to 20 hospitalization units from the Hospital Universitario de Burgos, who had experienced a fall in 2019 and were included in the register of falls from the GACELA Care® program. The form consisted of 28 data entry fields, and included information about date, time and place of the fall; reasons for falls; consequences of falls, and action by professionals. Descriptive and comparative analysis was conducted, using the relevant statistical tests. Results: in total, 244 (0.9%) falls were registered. The mean age was 73.3 years; 57.8% were male. The highest proportion of falls was recorded at Internal Medicine (29.1%) and Psychiatry (11.1%); 44.2% occurred during the night shift, in patients who were alone (71.7%); without protections (70.5%); and walking around (36.1%). The main reason was motor instability (48,4%); 62.7% of patients remained unharmed. There was a significant association between specialty and work shift and falls. Conclusions: there was a low prevalence of falls in the hospital. The factors associated with a higher proportion of falls were being >75-year-old, male gender, being admitted to medical specialty units, and night shift. Falls commonly occurred when the patient was alone, without protection, when getting up and walking. Most patients did not present any lesions.(AU)

Cryptic Diversity in Sympatric Migonemyia migonei (Diptera: Psychodidae), Eventual Meaning for Leishmaniasis Transmission.

Migonemyia migonei (FranÒ«a, 1920) (Diptera: Psychodidae) belongs to the subfamily Phlebotominae, of epidemiological importance due to its role as a vector in leishmaniasis transmission cycles and its broad geographic distribution in South America. Few morphometric and genetic studies have demonstrated the existence of variability among geographically distant populations in Brazil. The aim of the study was to estimate the genetic distance within the morphospecies Mg. migonei through the analysis of cytochrome C oxidase subunit I (COI) sequences of specimens captured in Argentina and those available in online databases. The COI sequences from specimens collected in different localities of Argentina and sequences available in online databases were utilized. Genetic distances were analyzed and a median-joining haplotype network was constructed. Finally, phylogenetic reconstruction was performed according to Bayesian inference. The analyses led to the identification of at least two haplogroups: haplogroup I with sequences of specimens from Colombia, Brazil and Argentina, and haplogroup II with sequences of specimens from Argentina. Interestingly, specimens from Argentina whose haplotypes corresponded to both haplogroups, were collected in sympatry. The results suggest that Mg. migonei could be a species complex with at least two distinct members. This hypothesis could explain the known characteristics of adaptability and vector permissiveness of the species, as the putative cryptic species of the complex could differ in traits of epidemiological importance.

Anticancer Drugs Compared to No Anticancer Drugs in Patients with Advanced Hepatobiliary Cancer: A Mapping Review and Evidence Gap Map.

Introduction: Despite being commonly recommended, the impact of anticancer drugs (ACDs) on patient-important outcomes beyond survival for advanced hepatobiliary cancers (HBCs) may not have been sufficiently assessed. We aim to identify and map the evidence regarding ACDs versus best supportive care (BSC) for advanced HBCs, considering patient-centered outcomes. Methods: In this mapping review, we included systematic reviews, randomized controlled trials, quasi-experimental, and observational studies comparing ACDs (chemotherapy, immunotherapy, biological/targeted therapy) versus BSC for advanced HBCs. We searched MEDLINE (PubMed), EMBASE (Ovid), Cochrane Library, Epistemonikos, PROSPERO and clinicaltrials.gov for eligible studies. Two reviewers performed the screening and data extraction processes. We developed evidence maps for each type of cancer. Results: We included 87 studies (60 for advanced liver cancer and 27 for gallbladder or bile duct cancers). Most of the evidence favored ACDs for survival outcomes, and BSC for toxicity. We identified several evidence gaps for non-survival outcomes, including quality of life or quality of end-of-life care. Discussion: Patient-important outcomes beyond survival in advanced HBCs are insufficiently assessed by the available evidence. Future studies need to address these gaps to better inform decision-making processes.

Understanding the Effect of Electron Beam Melting Scanning Strategies on the Aluminum Content and Materials State of Single Ti-6Al-4V Feedstock.

Research on the additive manufacturing of metals often neglects any characterization of the composition of final parts, erroneously assuming a compositional homogeneity that matches the feedstock material. Here, the composition of electron-beam-melted Ti-6Al-4V produced through three distinct scanning strategies (linear raster and two point melting strategies, random fill and Dehoff fill) is characterized both locally and globally through energy-dispersive spectroscopy and quantitative chemical analysis. As a result of the different scanning strategies used, differing levels of preferential vaporization occur across the various parts, leading to distinct final compositions, with extremes of ~5.8 wt.% Al and ~4.8 wt.% Al. In addition, energy-dispersive spectroscopy composition maps reveal specific features in both the XY and XZ planes (with Z being the build direction) as a result of local inhomogeneous preferential vaporization. The subsequent change in composition significantly modifies the materials' state of parts, wherein parts and local regions with higher aluminum contents lead to higher hardness levels (with a ~50 HV difference) and elastic property values and vice versa. While varying scan strategies and scan parameters are known to modify the microstructure and properties of a part, the effect on composition cannot, and should not, be neglected.

Study of the Electronic Interaction between NiO and Short Polythiophene Chains towards Solar Photon Harvesting.

The sustainable production of energy is a field of interest to which a new requirement is now imposed: the need to be respectful of the environment. New materials and techniques are being developed, but environmental concerns impose the necessity of keeping research active towards the development of green energy. For this reason, we present the study of short polythiophene (PTh) chains (three and five monomers) and their interaction with nickel oxide, looking for properties related to solar photon harvesting in order to produce electricity. The models of the molecules were developed, and the calculations were performed with an M11-L meta-GGA functional, specially developed for electronic structure calculations. The theoretical explorations demonstrated that the geometry of the PTh molecules suffer little distortion when interacting with the NiO molecule. The calculated value of Eg lies between 2.500 and 0.412 eV for a three-ring PTh chain and between 1.944 and 0.556 eV for a five-ring PTh chain. The chemical parameters indicated that, depending on the geometry of the system, the chemical potential varies from 81.27 to 102.38 kcal/mol and the highest amount of electronic charge varies from -2.94 to 21.56 a.u. for three-monomer systems. For five-monomer systems, the values lie within similar ranges as those of the three-monomer systems. The Partial Density of States (PDOS) showed that the valence and conduction electronic bands were composed of states in the NiO and PTh rings, except for a system where there was a non-bonding interaction.

High burden of asymptomatic malaria and anaemia despite high adherence to malaria control measures: a cross-sectional study among pregnant women across two seasons in a malaria-endemic setting in Ghana.

PURPOSE: Anaemia remains a serious concern among pregnant women, and thus, it is closely monitored from the onset of pregnancy through to delivery to help prevent adverse maternal and neonatal outcomes. In malaria-endemic settings, continuous low-level carriage of P. falciparum parasites is common and its contribution to maternal anaemia should not be underestimated. In this study, we evaluated the impact of adherence to malaria control measures [number of antenatal clinics (ANC) attended, supervised intake of sulphadoxine pyrimethamine (SP), and use of insecticide treated bed nets (ITNs)] on asymptomatic malaria and anaemia outcomes among pregnant women on ANC in hospitals in the Central region of Ghana. METHODS: The study was conducted during two seasons; October-November 2020 (dry season, n = 124) and May-June 2021 (rainy season, n = 145). Among the women, there was a high adherence to the control measures for both seasons (ANC ≥ 3 visits; ~ 82.0%, intake of SP; ~ 80.0% and ITNs use; ~ 75.0%). RESULTS: Asymptomatic P. falciparum carriage was high for both seasons (44.4% for the dry season; 46.9% for the rainy season). Correspondingly, the occurrence of anaemia was high for both seasons (57.3% for the dry season; 68.3% for the rainy season) and was strongly predicted by carriage of P. falciparum parasites. Despite the high adherence to ANC protocols, asymptomatic P. falciparum infection was common and contributed to the high burden of maternal anaemia. CONCLUSIONS: Our findings emphasize the need for improved control measures that can clear asymptomatic/sub-microscopic P. falciparum infection and protect against malaria-induced anaemia among pregnant women attending ANC in malaria endemic-settings.

Comparative analysis of systemic oncological treatments and best supportive care for advanced gastresophageal cancer: A comprehensive scoping review and evidence map.

OBJECTIVE: To identify, describe, and organize the available evidence regarding systemic oncological treatments compared to best supportive care (BSC) for advanced gastresophageal cancer. METHODS: We conducted a thorough search across MEDLINE (PubMed), EMbase (Ovid), The Cochrane Library, Epistemonikos, PROSPERO, and Clinicaltrials.gov. Our inclusion criteria encompassed systematic reviews, randomized controlled trials, quasi-experimental and observational studies involving patients with advanced esophageal or gastric cancer receiving chemotherapy, immunotherapy or biological/targeted therapy compared to BSC. The outcomes included survival, quality of life, functional status, toxicity, and quality of end-of-life care. RESULTS: We included and mapped 72 studies, comprising SRs, experimental and observational designs, 12 on esophageal cancer, 51 on gastric cancer, and 10 both locations. Most compared schemes including chemotherapy (47 studies), but did not report therapeutic lines. Moreover, BSC as a control arm was poorly defined, including integral support and placebo. Data favor the use of systemic oncological treatments in survival outcomes and BSC in toxicity. Data for outcomes including quality of life, functional status, and quality of end-of-life care were limited. We found sundry evidence gaps specifically in assessing new treatments such as immunotherapy and important outcomes such as functional status, symptoms control, hospital admissions, and the quality of end-life care for all the treatments. CONCLUSIONS: There are important evidence gaps regarding new for patients with advanced gastresophageal cancer and the effect of systemic oncological treatments on important patient-centered outcomes beyond survival. Future research should clearly describe the population included, specifying previous treatments and considering therapeutic, and consider all patient-centered outcomes. Otherwise, it will be complex to apply research results into practice.

DietaAnti-Inflamatoria or DAIN: A Crohn's disease management strategy tailored for Puerto Ricans.

Diet has been increasingly shown to be of therapeutic benefit for patients with inflammatory bowel diseases (IBD), especially Crohn's disease (CD). Yet dietary guidelines are nonexistent. Moreover, diets tailored to Puerto Ricans with IBD living on the island, have not been developed and tested. The rising prevalence of IBD in Puerto Rico warrants exploring the use of diet as part of the treatment strategies for these patients [1]. Here, we describe the study design of "Dieta Anti-Inflamatoria" or DAIN, a parallel two-arm randomized pilot trial aiming at testing the efficacy of IBD-Anti-inflammatory diet (IBD-AID) adapted for adults with CD living in Puerto Rico (clinical trial registration number: NCT05627128). We tailored the IBD-AID to the local cuisine preferences and food availability by creating and adapting recipes consistent with the IBD-AID principles [2,3]. In focus groups with a Community Research Advisory Panel and one-on-one consultations with implementation experts, we identified several aspects of the intervention to adapt before the implementation. The objectives of the stakeholder/expert-informed adaptation were to improve feasibility and compliance while developing the culturally tailored dietary intervention. DAIN was designed for adults living in Puerto Rico with CD and geared to be affordable, appropriate, and acceptable for patients with mild-to-moderate CD. The significance of this work is the validation of culturally appropriate nutritional guidelines to help manage CD symptoms. DAIN provides a blueprint for a comprehensive nutritional program that can be adapted to regional preferences and local food availability allowing wider implementation of diet as an adjunct treatment in diverse clinical settings.

Anti-phosphatidylserine antibody levels are low in multigravid pregnant women in a malaria-endemic area in Nigeria, and do not correlate with anti-VAR2CSA antibodies.

Anemia is a common malaria-associated complication in pregnant women in endemic regions. Phosphatidylserine (PS) is exposed to the immune system during the massive destruction of red blood cells (RBCs) that accompany malaria, and antibodies against PS have been linked to anemia through destruction of uninfected RBCs. We determined levels of anti-PS IgG antibodies in pregnant women in Ibadan, Nigeria and correlated them to parameters of importance in development of anemia and immunity. Anti-PS correlated inversely with Packed Cell Volume (PCV), indicating that the antibodies could contribute to anemia. There was no correlation with anti-VAR2CSA IgG, haptoglobin or parasitemia, indicating that the modulation of anti-PS response is multifactorial in nature. Anti-PS levels were lowest in multigravidae compared to both primigravidae and secundigravidae and correlated inversely with age. In conclusion, lower levels of anti-PS in multigravidae could be beneficial in avoiding anemia.

Systemic Oncological Treatments versus Supportive Care for Patients with Advanced Hepatobiliary Cancers: An Overview of Systematic Reviews.

BACKGROUND: The trade-off between systemic oncological treatments (SOTs) and UPSC in patients with primary advanced hepatobiliary cancers (HBCs) is not clear in terms of patient-centred outcomes beyond survival. This overview aims to assess the effectiveness of SOTs (chemotherapy, immunotherapy and targeted/biological therapies) versus UPSC in advanced HBCs. METHODS: We searched for systematic reviews (SRs) in PubMed, EMBASE, the Cochrane Library, Epistemonikos and PROSPERO. Two authors assessed eligibility independently and performed data extraction. We estimated the quality of SRs and the overlap of primary studies, performed de novo meta-analyses and assessed the certainty of evidence for each outcome. RESULTS: We included 18 SRs, most of which were of low quality and highly overlapped. For advanced hepatocellular carcinoma, SOTs showed better overall survival (HR = 0.62, 95% CI 0.55-0.77, high certainty for first-line therapy; HR = 0.85, 95% CI 0.79-0.92, moderate certainty for second-line therapy) with higher toxicity (RR = 1.18, 95% CI 0.87-1.60, very low certainty for first-line therapy; RR = 1.58, 95% CI 1.28-1.96, low certainty for second-line therapy). Survival was also better for SOTs in advanced gallbladder cancer. No outcomes beyond survival and toxicity could be meta-analysed. CONCLUSION: SOTs in advanced HBCs tend to improve survival at the expense of greater toxicity. Future research should inform other patient-important outcomes to guide clinical decision making.

The Rapid and Spontaneous Postpartum Clearance of Plasmodium falciparum Is Related to Expulsion of the Placenta.

Parasitemia among pregnant women with protective immunity to Plasmodium falciparum malaria is often dominated by VAR2CSA-positive infected erythrocytes (IEs). VAR2CSA mediates sequestration of IEs in the placenta. We hypothesized that the previously observed spontaneous postpartum clearance of parasitemia in such women is related to the expulsion of the placenta, which removes the sequestration focus of VAR2CSA-positive IEs. We assessed parasitemias and gene transcription before and shortly after delivery in 17 Ghanaian women. The precipitous decline in parasitemia postpartum was accompanied by selective reduction in transcription of the gene encoding VAR2CSA. Our findings provide a mechanistic explanation for the earlier observation.

Systemic oncological treatments in patients with advanced pancreatic cancer: a scoping review and evidence map.

PURPOSE: To identify, describe, and organise currently available evidence regarding systemic oncological treatments (SOTs) (chemotherapy, targeted/biological therapies, and immunotherapy) compared to best supportive care (BSC) for patients with advanced pancreatic cancer (PC). METHODS: We conducted a scoping review and evidence mapping, adhering to PRISMA-ScR checklist. We searched MEDLINE, EMBASE, Cochrane Library, Epistemonikos, PROSPERO, and clinicaltrials.gov for eligible studies. We included systematic reviews (SRs), randomised controlled trials (RCTs), quasi-experimental, and observational studies evaluating SOTs compared to BSC or no treatment in patients with advanced PC. Two independent reviewers performed the screening process and data extraction. We developed evidence maps as an interactive visualization display, including the assessed interventions and outcomes. RESULTS: Of the 50,601 records obtained from our search, we included 43 studies: 2 SRs, 16 RCTs, 4 quasi-experimental studies, 20 observational studies, and 1 protocol for a quasi-experimental study. Forty-two studies reported survival-related outcomes and most favoured SOTs, while five reported toxicity and most favoured BSC. Other patient-centred outcomes, such as quality of life, were scarcely reported. CONCLUSIONS: This study highlights the current evidence gaps in studies assessing treatments for patients with advanced PC, mainly the lack of reports of non-survival-related outcomes, pointing out research areas that need further attention to make better recommendations for these patients.

Household ovicidal alternative for complementary control of Aedes aegypti in the Gran San Miguel de Tucuman agglomerate, Tucumán, Argentina.

Aedes aegypti is closely related to human behavior that allows its establishment through the accumulation of urban solid waste where it lays resistant eggs. Generally, adulticides and larvicides are applied in excess, without ovicidal alternatives, and some household products can help reduce the abundance of quiescent eggs in breeding sites by affecting the viability of eggs. A community involved in prevention and control is one of the most effective strategies for adequate vector management. In this investigation, new alternative strategies for the control of Ae. aegypti are assessed, valuing in laboratory the eggs' response to diverse household products. Susceptibility to different doses of bleach, oil, salt, sodium bicarbonate, vinegar, coffee, garlic, peroxide, and alcohol was measured, as well as its duration over time. New home products were found as alternative ovicidal method. Bleach and sunflower oil had an ovicidal effect at their maximum doses and at almost all of the evaluation times. In contrast, vinegar and coffee had no ovicidal effect at any time, turning out to be stimulators of hatching in the laboratory. These alternative and complementary applications could optimize the surveillance and control of Ae. aegypti in the area, allowing new approaches to reduce populations by eliminating eggs on human microhabitats.

The value of sentinel lymph-node biopsy in women with node-positive breast cancer at diagnosis and node-negative tumour after neoadjuvant therapy: a systematic review.

PURPOSE: To conduct a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) in women with node-positive breast cancer at diagnosis and node-negative tumour after neoadjuvant therapy, compared to axillary lymph-node dissection. METHODS: The more relevant databases were searched. Main outcomes were false-negative rate (FNR), sentinel lymph-node identification rate (SLNIR), negative predictive value (NPV), and accuracy. We conducted meta-analyses when appropriate. RESULTS: Twenty studies were included. The pooled FNR was 0.14 (95% CI 0.11-0.17), the pooled SLNIR was 0.89 (95% CI 0.86-0.92), NPV was 0.83 (95% CI 0.79-0.87), and summary accuracy was 0.92 (95% CI 0.90-0.94). SLNB performed better when more than one node was removed and double mapping was used. CONCLUSIONS: SLNB can be performed in women with a node-negative tumour after neoadjuvant therapy. It has a better performance when used with previous marking of the affected node and with double tracer.

Analysis of combined non-invasive respiratory support in the first six waves of the COVID-19 pandemic. Outcome according to the first respiratory support.

Introduction: COVID-19 can lead to acute respiratory failure (ARF) requiring admission to intensive care unit (ICU). This study analyzes COVID-19 patients admitted to the ICU, according to the initial respiratory support. Its main aim is to determine if the use of combination therapy: high-flow oxygen system with nasal cannula (HFNC) and non-invasive ventilation (NIV), is effective and safe in the treatment of these patients. Methods: Retrospective observational study with a prospective database. All COVID-19 patients, admitted to the ICU, between March 11, 2020, and February 12, 2022, and who required HFNC, NIV, or endotracheal intubation with invasive mechanical ventilation (ETI-IMV) were analyzed. HFNC failure was defined as therapeutic escalation to NIV, and NIV failure as the need for ETI-IMV or death in the ICU. The management of patients with non-invasive respiratory support included the use of combined therapy with different devices. The study period included the first six waves of the pandemic in Spain. Results: 424 patients were analyzed, of whom 12 (2.8%) received HFNC, 397 (93.7%) NIV and 15 (3.5%) ETI-IMV as first respiratory support. PaO2/FiO2 was 145 ± 30, 119 ± 26 and 117 ± 29 mmHg, respectively (p = 0.003). HFNC failed in 11 patients (91.7%), who then received NIV. Of the 408 patients treated with NIV, 353 (86.5%) received combination therapy with HFNC. In patients treated with NIV, there were 114 failures (27.9%). Only the value of SAPS II index (p = 0.001) and PaO2/FiO2 (p < 0.001) differed between the six analyzed waves, being the most altered values in the 3rd and 6th waves. Hospital mortality was 18.7%, not differing between the different waves (p = 0.713). Conclusions: Severe COVID-19 ARF can be effectively and safely treated with NIV combined with HFNC. The clinical characteristics of the patients did not change between the different waves, only showing a slight increase in severity in the 3rd and 6th waves, with no difference in the outcome.

Cryo-EM reveals the conformational epitope of human monoclonal antibody PAM1.4 broadly reacting with polymorphic malarial protein VAR2CSA.

Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Immunity to placental malaria is acquired through exposure and mediated through antibodies to VAR2CSA. Through evolution, the VAR2CSA proteins have diversified in sequence to escape immune recognition but retained their overall macromolecular structure to maintain CS binding affinity. This structural conservation may also have allowed development of broadly reactive antibodies to VAR2CSA in immune women. Here we show the negative stain and cryo-EM structure of the only known broadly reactive human monoclonal antibody, PAM1.4, in complex with VAR2CSA. The data shows how PAM1.4's broad VAR2CSA reactivity is achieved through interactions with multiple conserved residues of different sub-domains forming conformational epitope distant from the CS binding site on the VAR2CSA core structure. Thus, while PAM1.4 may represent a class of antibodies mediating placental malaria immunity by inducing phagocytosis or NK cell-mediated cytotoxicity, it is likely that broadly CS binding-inhibitory antibodies target other epitopes at the CS binding site. Insights on both types of broadly reactive monoclonal antibodies may aid the development of a vaccine against placental malaria.

Boosted Activity of g-C3N4/UiO-66-NH2 Heterostructures for the Photocatalytic Degradation of Contaminants in Water.

The combination of graphitic carbon nitride and the metal-organic framework UiO-66-NH2 has been developed with the aim to enhance the photocatalytic activity of pure semiconductors. Different proportions of g-C3N4 and UiO-66-NH2 were combined. Complete characterization analysis of the resulting photocatalytic materials was conducted, including N2 adsorption isotherms, XRD, FTIR, STEM-EDX microscopy, DRS-UV-visible, and photoluminescence. The photocatalytic activity was tested in an aqueous solution for the removal of acetaminophen as the target pollutant. From the obtained results, less than 50% of UiO-66-NH2 incorporated in the g-C3N4 structure enhanced the photocatalytic degradation rate of both bare semiconductors. Concretely, 75% of g-C3N4 in the final g-C3N4/UiO-66-NH2 heterostructure led to the best results, i.e., complete acetaminophen elimination initially at 5 mg·L-1 in 2 h with a pseudo-first order rate constant of ca. 2 h-1. The presence of UiO-66-NH2 in the g-C3N4 enhanced the optoelectronic properties, concretely, the separation of the photo-generated charges was improved according to photoluminescence characterization. The better photo-absorption uptake was also confirmed by the determination of the quantum efficiency values of the heterostructure if compared to either pure g-C3N4 or UiO-66-NH2. This photocatalyst with the best activity was further tested at different pH values, with the best degradation rate at a pH close to the pHpzc ~4.15 of the solid. Sequential recycling tests demonstrated that the heterostructure was stable after five cycles of use, i.e., 15 h. A high contribution of photo-generated holes in the process of the degradation of acetaminophen, followed marginally by superoxide radicals, was suggested by scavenger tests.