Search

With the increasing challenge to shift our economic system from carbon to renewable energy carriers, the demand for biogenic resources is growing. Biogenic municipal waste, agricultural by-products and industrial residues are under-utilised but are increasingly gaining in value. To date, there is no continuous database for these resources in the EU-27 countries. Existing datasets that estimate resource potentials for a single point in time often lack validation. A reliable and continuous database is thus needed to support the growing bioeconomy. Spatial and temporal high-resolution data of biogenic residues serve as an invaluable resource for identifying areas with significant theoretical biomass potential and allows an in-depth understanding of dynamic patterns over time. This study elucidates the theoretical biomass potentials of 13 distinct biomasses from municipal waste, agricultural by-products and industrial residues quantified annually from 2010–2020. The spatial scope of the research covers the EU-27 Member States incorporating all entities represented at various levels within the Nomenclature of Territorial Units for Statistics (NUTS) as delineated by Eurostat, where possible. The regionalised data are subsequently validated against regional statistics from different countries. The findings demonstrate the feasibility of creating a time series of theoretical biomass potentials for the 13 selected waste types, by-products, and residues, and underscore the critical role of data validation when regionalising national or sub-national data to smaller NUTS entities. It could be shown that the values of small regions (NUTS 3) correlated well on average. When looking at individual regions in detail, regional characteristics such as the location of cultivation, waste management or reporting methods could lead to over- or underestimates of up to 100 %. Therefore, data at the regional level provide only limited reliability. In the case of industrial residues, regionalisation gave good results localising preference regions of high theoretical biomass potential, but more data on industrial production are needed to also estimate residual quantities at sub-national and local levels. The biomass potentials modelled in this study have been published in an open-access database, which is designed as an extensible tool, enabling the understanding of national and regional trends of theoretical biomass potentials in the European Union and of the reliability of the regionalised data. The estimated theoretical potential dataset can be downloaded free of charge from: https://doi.org/10.48480/g53t-ks72 (Günther et al., 2023).

Rationale: Nox4 is a constitutively active NADPH oxidase that constantly produces low levels of H2O2. Thereby, Nox4 contributes to cell homeostasis and long-term processes, such as differentiation. The high expression of Nox4 seen in endothelial cells contrasts with the low abundance of Nox4 in stem cells, which are accordingly characterized by low levels of H2O2. We hypothesize that Nox4 is a major contributor to endothelial differentiation, is induced during the process of differentiation, and facilitates homeostasis of the resulting endothelial cells. Objective: To determine the role of No×4 in differentiation of murine inducible pluripotent stem cells (miPSC) into endothelial cells (ECs). Methods and results: miPSC, generated from mouse embryonic wildtype (WT) and Nox4−/− fibroblasts, were differentiated into endothelial cells (miPSC-EC) by stimulation with BMP4 and VEGF. During this process, Nox4 expression increased and knockout of Nox4 prolonged the abundance of pluripotency markers, while expression of endothelial markers was delayed in differentiating Nox4-depleted iPSCs. Eventually, angiogenic capacity of iPSC-ECs is reduced in Nox4 deficient cells, indicating that an absence of Nox4 diminishes stability of the reached phenotype. As an underlying mechanism, we identified JmjD3 as a redox target of Nox4. iPSC-ECs lacking Nox4 display a lower nuclear abundance of the histone demethylase JmjD3, resulting in an increased triple methylation of histone 3 (H3K27me3), which serves as a repressive mark for several genes involved in differentiation. Conclusions: Nox4 promotes differentiation of miPSCs into ECs by oxidation of JmjD3 and subsequent demethylation of H3K27me3, which forced endothelial differentiation and stability.

T cell responses are known to be essential in the immune response to Ebola virus infection, and the viral glycoprotein is a major antigenic target. Here the authors provide fine detail mapping of T cell antigens and their characterisation in Ebola virus survivor patients.

Abstract Background As early as pregnancy, maternal mental stress impinges on the child’s development and health. Thus, this may cause enhanced risk for premature birth, lowered fetal growth, and lower fetal birth weight as well as enhanced levels of the stress hormone cortisol and lowered levels of the bonding hormone oxytocin. Maternal stress further reduces maternal sensitivity for the child’s needs which impairs the mother-child-interaction and bonding. Therefore, prevention and intervention studies on mental stress are necessary, beginning prenatally and applying rigorous research methodology, such as randomized controlled trials, to ensure high validity. Methods A randomized controlled trial is used to assess the impact of psychotherapy and telemedicine on maternal mental stress and the child’s mental and physical health. Mentally stressed pregnant women are randomized to an intervention (IG) and a not intervened control group. The IG receives an individualized psychotherapy starting prenatal and lasting for 10 months. Afterwards, a second randomization is used to investigate whether the use of telemedicine can stabilize the therapeutic effects. Using ecological momentary assessments and video recordings, the transfer into daily life, maternal sensitivity and mother-child-bonding are assessed. Psycho-biologically, the synchronicity of cortisol and oxytocin levels between mother and child are assessed as well as the peptidome of the colostrum and breast milk, which are assumed to be essential for the adaptation to the extra-uterine environment. All assessments are compared to an additional control group of healthy women. Finally, the results of the study will lead to the development of a qualification measure for health professionals to detect mental stress, to treat it with low-level interventions and to refer those women with high stress levels to mental health professionals. Discussion The study aims to prevent the transgenerational transfer of psychiatric and somatic disorders from the mother to her child. The effects of the psychotherapy will be stabilized through telemedicine and long-term impacts on the child’s and mothers’ mental health are enhanced. The combination of psychotherapy, telemedicine and methodologies of ecological momentary assessment, video recording and bio banking are new in content-related and methodological manner. Trial registration German Clinical Trials Register: DRKS00017065. Registered 02 May 2019. World Health Organization, Universal Trial Number: U1111–1230-9826. Registered 01 April 2019.

GPCRs are key regulators of vascular functions. By analysing single-cell GPCRs expression in vascular smooth muscle and endothelial cells from healthy and diseased murine vessels, Kauret al. show that GPCR expression is highly heterogeneous in all cell types and that disease causes GPCR repertoire changes depending on cell type and vascular localization.

The original version of this Article omitted the following from the Acknowledgements: ‘This project was supported by CRC128/Project A03 of the Deutsche Forschungsgemeinschaft (DFG).’This has not been corrected in either the PDF or HTML versions.

Study Design: This is an experiential article based on the past 6 years experience of providing facial gender confirmation surgery (fGAS) at an academic medical center., Objective: While trainees are getting increasing exposure to aspects of facial gender affirming surgery (fGAS), the gap between trained providers and patients who can access care is currently still widening. A handful of fellowships across the country have emerged that include fGAS in their curriculum, but it will take another decade before the principles of affirming care and surgeries are systematically taught. Fortunately, the surgical principles and techniques required to perform fGAS are part of the skill set of any specialty surgeon trained in adult craniofacial trauma and esthetic facial surgery/rhinoplasty. It is the aim of this article to provide directly applicable knowledge with the goal to assist surgeons who consider offering fGAS in flattening the learning curve and hopefully contribute to increasing the quality of care provided for the transgender and gender diverse population. We hope to provide the reader with a very tangible article with the aims to 1) provide a simple systematic framework for an affirming consultation and preoperative assessment and 2) provide translatable surgical pearls and pitfalls for forehead feminization and gonial angle resection. The frontal sinus set back and gonial angle resection in our opinion are the most unique aspect to fGAS as rhinoplasty, genioplasty and other associated procedures (e.g., fat grafting) follow well established principles. We hope that the value of this article lies in the translatability of the presented principle to any practice setting without the need for VSP, special surgical instruments or technology beyond basic craniofacial tools., Methods: This is an experiential article based on the senior authors 6 year experience offering fGAS in an academic setting. The article is structured to outline both pearls and pittfalls and is supplemented by photographs and a surgical video., Results: A total of 19 pearls and pitfalls are outlined in the article., Conclusions: Facial gender affirming surgery mostly follows established craniofacial and esthetic surgery principles. Forehead feminization and gonial angle feminization are the 2 components that diverge most from established surgical techniques and this article hopefully provides guidance to shorten the learning curve of surgeons., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Cotard syndrome is a rare presentation where patients present with nihilistic thoughts of dying or already being dead. These delusions manifest from either a medical or psychiatric etiology and can be difficult to treat. Recently Couto and Gonçalves purposed that treatment should include an atypical antipsychotic alone or in combination with either a mood stabilizer or antidepressant. Here the authors advocate for a more specific but well-known psychotropic regimen, namely the combination of olanzapine and fluoxetine. We conducted a literature review and of 246 papers identified, only three reported using a combination of fluoxetine and olanzapine with many of them having limited or confounding information that make it difficult for us to comment on the historically efficacy of this medication combination. Therefore, the authors provide two case examples of patients being treated successfully with olanzapine and fluoxetine. One, a 66-year-old male veteran and another 76-year-old male veteran. Both of these cases hold significance as the patient's psychotic depression was so severe as to warrant ECT as a possible treatment. In both cases, this medication combination was able to avoid the procedure. Overall, with the addition of our cases and the sparse information available in the literature, we propose the combination of fluoxetine and olanzapine as an effective Cotard syndrome treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Adam J. Fusick et al.)

Background: Lipomas are a rare cause of posterior interosseous nerve (PIN) compression. A systematic review of predictors for motor recovery has not been performed. This study sought to evaluate whether patient or lipoma characteristics are associated with motor recovery and could be used to determine when immediate tendon transfers at the time of excision should be performed., Methods: Articles describing patients with forearm lipomas resulting in PIN compression with motor weakness were included. Patient age, gender, symptom duration, laterality and largest dimension of lipoma, surgical intervention, and motor recovery were identified. Article quality was assessed via the Methodological Index for Non-Randomized Studies criteria., Results: Thirty articles reporting on 34 patients were identified. Average age was 58.2 years. Average largest lipoma dimension was 5.7 cm. All patients underwent lipoma removal, and 2 had concomitant tendon transfers. In all, 73.5% of patients had complete motor recovery at an average of 9.7 months. Patient age and largest dimension of lipoma, and duration of symptoms were not significant predictors of motor recovery. Symptom duration was a significant predictor of motor recovery in binary regression, particularly if < 18 months., Conclusions: The majority of patients with PIN weakness secondary to lipoma are likely to have complete motor recovery after excision alone. Concomitant tendon transfers should be considered for patients symptomatic for greater than 18 months. Further, adequately powered, studies are required to stratify risk factors and evaluate other modalities to identify the minority of patients who would benefit from immediate tendon transfer., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KC is a consultant for Checkpoint Surgical. Cleveland, OH. CC, AP, SG declare that they have no conflict of interest.

Background: There is limited epidemiological evidence on Lassa fever in pregnant women with acute gaps on prevalence, infection incidence, and risk factors. Such evidence would facilitate the design of therapeutic and vaccine trials and the design of control programs. Our study sought to address some of these gaps by estimating the seroprevalence and seroconversion risk of Lassa fever in pregnant women., Methodology/principal Findings: We conducted a prospective hospital-based cohort between February and December 2019 in Edo State, Southern Nigeria, enrolling pregnant women at antenatal clinic and following them up at delivery. Samples were evaluated for IgG antibodies against Lassa virus. The study demonstrates a seroprevalence of Lassa IgG antibodies of 49.6% and a seroconversion risk of 20.8%. Seropositivity was strongly correlated with rodent exposure around homes with an attributable risk proportion of 35%. Seroreversion was also seen with a seroreversion risk of 13.4%., Conclusions/significance: Our study suggests that 50% of pregnant women were at risk of Lassa infection and that 35.0% of infections might be preventable by avoiding rodent exposure and conditions which facilitate infestation and the risk of human-rodent contact. While the evidence on rodent exposure is subjective and further studies are needed to provide a better understanding of the avenues of human-rodent interaction; public health measures to decrease the risk of rodent infestation and the risk of spill over events may be beneficial. With an estimated seroconversion risk of 20.8%, our study suggests an appreciable risk of contracting Lassa fever during pregnancy and while most of these seroconversions may not be new infections, given the high risk of adverse outcomes in pregnancy, it supports the need for preventative and therapeutic options against Lassa fever in pregnancy. The occurrence of seroreversion in our study suggests that the prevalence obtained in this, and other cohorts may be an underestimate of the actual proportion of women of childbearing age who present at pregnancy with prior LASV exposure. Additionally, the occurrence of both seroconversion and seroreversion in this cohort suggests that these parameters would need to be considered for the development of Lassa vaccine efficacy, effectiveness, and utility models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kayem et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Evidence from previous studies suggest that Lassa fever, a viral haemorrhagic fever endemic to West Africa has high case fatalities, particularly in pregnancy. While there have been remarkable innovations in vaccine development, with some Lassa vaccines undergoing early clinical trials. An understanding of Lassa antibody kinetics and immune responses will support vaccine design and development. However, there is currently no evidence on the antibody kinetics of Lassa (LASV) in pregnancy. Our study sought to estimate the efficiency of transplacental transfer of LASV IgG antibodies from the mother to the child., Methodology/principal Findings: The study made use of data from a prospective hospital-based cohort of pregnant women enrolled at the antenatal clinic and followed up at delivery between February and December 2019. Blood samples from mother-child pairs were evaluated for antibodies against Lassa virus. The study demonstrates a transplacental transfer of LASV IgG of 75.3% [60.0-94.0%], with a significant positive correlation between maternal and cord concentrations and a good level of agreement. The study also suggests that transfer may be more variable in women with 'de novo' antibodies compared to those with pre-existing antibodies., Conclusions/significance: The study shows that maternal antibody levels play an important role in determining transfer efficiency of Lassa antibodies to the new-born; and while the evidence is preliminary, the study also suggests that transfer efficiency may be less stable in acute or recent infection, as such timing of vaccination before pregnancy, that is in women of childbearing age may be more appropriate for protection of both pregnant women and their neonates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kayem et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Idiopathic pulmonary fibrosis (IPF) is a severe, progressive and irreversible lung disease constantly associated with a major vascular remodeling process. Endothelial colony-forming cells (ECFCs) are human vasculogenic cells proposed as a cell therapy product or liquid biopsy in vascular disorders. Since the link between IPF and thrombosis has been largely proposed, the aim of our study was to explore hypercoagulability states in ECFCs from patients with IPF. We performed Thrombin generation assay (TGA) in cord blood (CB)-ECFCs, peripheral blood (PB)-ECFCs and IPF-ECFCs. Endogenous thrombin potential and peak were higher in IPF-ECFCs compared to CB-ECFCs and PB-ECFCs. As thrombin generation in ECFCs was increased, we evaluated anticoagulant proteins expressed on ECFCs membrane and identified thrombomodulin and EPCR. We found a significant decrease of both anticoagulant proteins at membrane using flow cytometry. This study is the first to examine ECFC thrombin generation in IPF. This new finding strongly argues for a role of ECFC in IPF pathophysiology and thrombotic related disorders in IPF. Graphical Abstract.

Intermetallic porous SHS-TiNi alloys exhibit tangled and specific stress-strain characteristics. This article aims to evaluate the findings emanating from experiments using standard and proprietary instruments. Fatigue testing under repeated complex loading was used to measure the total number of load cycles before failure of the SHS-TiNi samples occurred. Of the tested samples, seventy percent passed through 10 6 cycles without failure due to the reversible martensite transformation in the TiNi phase, one of the prevailing constituents of a multiphase matrix. The fractured surfaces were analyzed using scanning electron microscopy and confocal laser scanning instruments. Microscopy studies showed that the entire surface of the sample is concealed by miscellaneous strata that result from the SHS processand effectively protect the porous alloy in a corrosive environment. Numerous non-metallic inclusions, which are also attributed to the SHS reaction, do not have a significant impact on the deformation behavior and fatigue performance. In this context, the successful in vivo functioning of porous grafts assessed in a canine rib-plasty model allows the bone substitute to be congruentially deformed in the body without rejection or degradation; it thus has a long operational life, often greater than 17 ×10 6 (22 × 60 × 24 × 540) cycles. It acknowledges the potential benefits of SHS-TiNi as a superior osteoplastic material and its high resistance to corrosion fatigue.

Background: During rhinoplasty, it is typically necessary to use cartilage to shape and support the final nasal construct to provide both form and function to the nose (Tanna et al. in Plast Reconstr Surg 141(1):137e-151e, 2018; Guyuron in Plast Reconstr Surg 105(6):2257-2259, 2000; Kim et al. in Ann Plast Surg 65(6):519-523, 2010). The septal cartilage is the ideal graft both for its ease of access and quality of cartilage. However, this graft is a limited resource, and economy of its use is important as to negate the need to harvest cartilage from the ear or rib., The Purpose: 1. To share the senior author's 40 years' experience with the economy of septal cartilage. 2. To identify the areas of the septal cartilage most suitable for a particular graft. 3. To discuss the common grafts that are used in rhinoplasty. 4. To identify when other sources of cartilage are needed and where to best use those grafts. 5. To present option for preservation of the leftover septal cartilage., Conclusion: Overall consideration should focus on the size, thickness, and curvature of the graft contemplating the structural and functional needs of the rhinoplasty maneuvers., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Strain CS-1 T , a novel facultative anaerobic bacterium, was isolated from the larval gastrointestinal tract of the biting midge, Culicoides sonorensis , a vector of the epizootic haemorrhagic disease virus and the bluetongue virus. Cells were Gram-stain-positive, non-motile, non-spore-forming, pleomorphic rods. Optimal growth occurred at pH 7.5 and 37 °C. The G+C content of the genomic DNA was 38.3 mol%, estimated by using HPLC. The dominant cellular fatty acids were C 14 : 0 (45.9 %) and C 16 : 0 (26.6 %). The polar lipid profile comprised glycolipids, diphosphatidylglycerol, phospholipids and phosphoglycolipids. Respiratory quinones were not detected. Strain CS-1 T had very low 16S rRNA gene similarity to members of the phylum Firmicutes : Macrococcus canis KM45013 T (85 % similarity) and Turicibacter sanguinis MOL361 T (88 % similarity). Phylogenetic analysis based on 16S rRNA, rpoB, gyrB genes, and conserved protein sequences of the whole genome revealed that strain CS-1 T was related to members of the classes Bacilli and Erysipelotrichia within the phylum Firmicutes . Furthermore, average nucleotide identity and digital DNA-DNA hybridization analyses of the whole genome revealed very low sequence similarity to species of Bacilli and Erysipelotrichaceae ( Macrococcus canis KM45013 T and Turicibacter sp. H121). These results indicate that strain CS-1 T belongs to the phylum Firmicutes and represents a new species of a novel genus, family, order and class. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic characteristics, we propose the novel taxon Culicoidibacter larvae gen. nov., sp. nov. with the type strain CS-1 T (=CCUG 71726 T =DSM 106607 T ) within the hereby new proposed novel family Culicoidibacteraceae fam. nov., new order Culicoidibacaterales ord. nov. and new class Culicoidibacteria classis nov. in the phylum Firmicutes .

We report two outbreaks of Lassa fever that occurred in Benin in 2014 and 2016 with 20 confirmed cases and 50% (10/20) mortality. Benin was not previously considered to be an endemic country for Lassa fever, resulting in a delay to diagnose the disease and its human transmission. Molecular investigations showed the viral genomes to be similar to that of the Togo strain, which is genetically very different from other known strains and confirms the existence of a new lineage. Endemic circulation of Lassa virus in a new territory and the genetic diversity thus confirm that this virus represents a growing threat for West African people. Given the divergence of the Benin strain from the prototypic Josiah Sierra Leone strain frequently used to generate vaccine candidates, the efficacy of vaccine candidates should also be demonstrated with this strain.

Porous TiNi alloys fabricated by self-propagating high-temperature synthesis (SHS) are biomaterials designed for medical application in substituting tissue lesions and they were clinically deployed more than 30 years ago. The SHS process, as a very fast and economically justified route of powder metallurgy, has distinctive features which impart special attributes to the resultant implant, facilitating its integration in terms of bio-mechanical/chemical compatibility. On the phenomenological level, the fact of high biocompatibility of porous SHS TiNi (PTN) material in vivo has been recognized and is not in dispute presently, but the rationale is somewhat disputable. The features of the SHS TiNi process led to a multifarious intermetallic Ti 4 Ni 2 (O,N,C)-based constituents in the amorphous-nanocrystalline superficial layer which entirely conceals the matrix and enhances the corrosion resistance of the unwrought alloy. In the current article, we briefly explore issues of the high biocompatibility level on which additional studies could be carried out, as well as recent progress and key fields of clinical application, yet allowing innovative solutions.

Background: Gender confirming primary breast augmentation is becoming more common. The purpose of this study was to compare the demographic and anatomical differences in cis-female and trans-female populations., Methods: This was a retrospective analysis of trans-female patients and cis-female patients undergoing primary breast augmentation at a single institution. Analysis included patient demographics and preoperative chest measurements including sternal notch to nipple distance (SSN), breast width (BW), nipple to inframammary fold distance (N-IMF), and nipple to midline distance (N-M). Continuous variables were compared using independent t tests, and discrete variables were compared using Pearson's χ 2 tests., Results: Eighty-two trans-female and 188 cis-female patients undergoing primary breast augmentation were included. Trans-female patients were older (40.37 versus 34.07), more likely to have psychological comorbidities (50% versus 12.23%), and had a higher body mass index, 27.46 kg/m 2 versus 22.88 kg/m 2 ( P = 1.91E-07), than cis-female patients. Cis-female patients most commonly had an ectomorph body habitus (52% versus 26%), whereas trans-female patients most commonly had an endomorph body habitus (40% versus 7%). Pseudoptosis or ptosis was more commonly seen in cis-female patients ( P = 0.0056). There were significant differences in preoperative breast measurements including sternal notch to nipple distance, BW, and N-M between groups, but not in N-IMF. The ratio of BW/N-IMF was statistically significant ( P = 2.65E-07 on right), indicating that the similarity in N-IMF distance did not adjust for the difference in BW., Conclusions: The trans-female and cis-female populations seeking primary breast augmentation have significant demographic and anatomical differences. This has implications for surgical decision-making and planning to optimize outcomes for trans-female patients.

Background: Proper evaluation and analysis of speech surgery outcomes for cleft-related velopharyngeal incompetence in children and young adults performed on humanitarian missions is poorly characterized. The aim of this study is to examine the effect of using a multidisciplinary team on cleft-related humanitarian missions. The effect on patient selection, velopharyngeal mechanism imaging, and speech outcomes after surgery will be highlighted., Methods: A review of the Medical Readiness Training Exercise database for craniofacial missions to the Dominican Republic from 2009 to 2011 was performed. A speech pathologist and a craniofacial surgeon evaluated all patients with a diagnosis of cleft palate and speech abnormalities. Patients were screened using speech analysis and selective nasal endoscopy. Data collected included sex, age, diagnosis, speech scores, date, and type of surgical procedure-that is, pharyngeal flap (PF) versus sphincter pharyngoplasty (SP), morbidity, and mortality., Results: One hundred twenty-six patients with cleft palate were screened during the study period by a craniofacial surgeon and secondarily by a speech pathologist. Twenty-eight patients were identified with nasal quality speech of whom 12 patients (12/126 = 9.5% of total surgical cases) underwent PF/SP surgery after previous primary repair of a cleft palate defect. The 16 remaining patients (16/28 = 57%) with nonsurgical speech abnormalities were determined that surgery was not going to be beneficial and they were spared unnecessary surgery after speech pathology evaluation and nasal endoscopy. Eight patients were female and 4 patients were male; average age was 13.3 years (range 4-27 years). Seven pharyngeal flaps (58%) and 5 (42%) sphincter pharyngoplasty procedures were performed. The average presurgical speech score was 11.4 (range 6-24). There was a significant decrease in postsurgical speech scores with the average postsurgical speech score of 5.2 (range 0-21, P value = 0.0028). Follow-up evaluation averaged 18 months (range 6-24). Average hospital stay was 2 days for PF/SP surgery. Two patients, both with developmental delay, retained speech scores greater than 6. There were no major complications or reoperations., Conclusions: Pharyngeal flap/sphincter pharyngoplasty surgery in young adults resulted in improved speech scores and comprehensibility after speech surgery on Medical Readiness Training Exercise military humanitarian missions. Speech surgery in older patients in relatively austere environments is safe and effective. After comprehensive multidisciplinary team evaluation, 43% of the patients who were screened to have velopharyngeal incompetence were identified as surgical candidates. Fifty-seven percent of patients evaluated by speech pathologist were recommend nonsurgical solution toward improving speech scores sparing them unnecessary surgery. The incorporation of a speech pathologist to the humanitarian mission resulted in identifying surgical candidates who would benefit the most from intervention and improved speech surgery outcomes.

Background: Despite repeated outbreaks, in particular the devastating 2014-2016 epidemic, there is no effective treatment validated for patients with Ebola virus disease (EVD). Among the drug candidates is the broad-spectrum polymerase inhibitor favipiravir, which showed a good tolerance profile in patients with EVD (JIKI trial) but did not demonstrate a strong antiviral efficacy. In order to gain new insights into the antiviral efficacy of favipiravir and improve preparedness and public health management of future outbreaks, we assess the efficacy achieved by ascending doses of favipiravir in Ebola-virus-infected nonhuman primates (NHPs)., Methods and Findings: A total of 26 animals (Macaca fascicularis) were challenged intramuscularly at day 0 with 1,000 focus-forming units of Ebola virus Gabon 2001 strain and followed for 21 days (study termination). This included 13 animals left untreated and 13 treated with doses of 100, 150, and 180 mg/kg (N = 3, 5, and 5, respectively) favipiravir administered intravenously twice a day for 14 days, starting 2 days before infection. All animals left untreated or treated with 100 mg/kg died within 10 days post-infection, while animals receiving 150 and 180 mg/kg had extended survival (P < 0.001 and 0.001, respectively, compared to untreated animals), leading to a survival rate of 40% (2/5) and 60% (3/5), respectively, at day 21. Favipiravir inhibited viral replication (molecular and infectious viral loads) in a drug-concentration-dependent manner (P values < 0.001), and genomic deep sequencing analyses showed an increase in virus mutagenesis over time. These results allowed us to identify that plasma trough favipiravir concentrations greater than 70-80 μg/ml were associated with reduced viral loads, lower virus infectivity, and extended survival. These levels are higher than those found in the JIKI trial, where patients had median trough drug concentrations equal to 46 and 26 μg/ml at day 2 and day 4 post-treatment, respectively, and suggest that the dosing regimen in the JIKI trial was suboptimal. The environment of a biosafety level 4 laboratory introduces a number of limitations, in particular the difficulty of conducting blind studies and performing detailed pharmacological assessments. Further, the extrapolation of the results to patients with EVD is limited by the fact that the model is fully lethal and that treatment initiation in patients with EVD is most often initiated several days after infection, when symptoms and high levels of viral replication are already present., Conclusions: Our results suggest that favipiravir may be an effective antiviral drug against Ebola virus that relies on RNA chain termination and possibly error catastrophe. These results, together with previous data collected on tolerance and pharmacokinetics in both NHPs and humans, support a potential role for high doses of favipiravir for future human interventions.

Hypoxia mediates resistance to radio(chemo)therapy (RT) by stimulating the synthesis of hypoxia-related genes, such as osteopontin (OPN) and stress proteins, including the major stress-inducible heat shock protein 70 (Hsp70). Apart from its intracellular localization, Hsp70 is also present on the plasma membrane of viable tumor cells that actively release it in lipid vesicles with biophysical characteristics of exosomes. Exosomal Hsp70 contributes to radioresistance while Hsp70 derived from dying tumor cells can serve as a stimulator of immune cells. Given these opposing traits of extracellular Hsp70 and the unsatisfactory outcome of locally advanced lung tumors, we investigated the role of Hsp70 in the plasma of patients with advanced, non-metastasized non-small-cell lung cancer (NSCLC) before (T1) and 4-6 weeks after RT (T2) in relation to OPN as potential biomarkers for clinical response. Plasma levels of Hsp70 correlate with those of OPN at T1, and high OPN levels are significantly associated with a decreased overall survival (OS). Due to a therapy-induced reduction in viable tumor mass after RT Hsp70 plasma levels dropped significantly at T2 ( p  = 0.016). However, with respect to the immunostimulatory capacity of Hsp70 derived from dying tumor cells, patients with higher post-therapeutic Hsp70 levels showed a significantly better response to RT ( p  = 0.034) than those with lower levels at T2. In summary, high OPN plasma levels at T1 are indicative for poor OS, whereas elevated post-therapeutic Hsp70 plasma levels together with a drop of Hsp70 between T1 and T2, successfully predict favorable responses to RT. Monitoring the dynamics of Hsp70 in NSCLC patients before and after RT can provide additional predictive information for clinical outcome and therefore might allow a more rapid therapy adaptation.

Background: rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa., Methods: We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×10 7 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6-17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193., Findings: In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9-100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3-100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae., Interpretation: The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters., Funding: WHO, UK Wellcome Trust, the UK Government through the Department of International Development, Médecins Sans Frontières, Norwegian Ministry of Foreign Affairs (through the Research Council of Norway's GLOBVAC programme), and the Canadian Government (through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development)., (Copyright © 2017 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Bariatric surgery has emerged as an effective method of combating the morbid obesity epidemic. However, the massive weight loss that follows may result in contour changes that can affect body image and quality of life. Our study examines the effects and consequences of bariatric surgery and subsequent body contouring on body image and quality of life., Methods: Patients were prospectively followed up through their experience with bariatric surgery and subsequent body contouring surgery. Using 2 validated survey instruments, the Multidimensional Body-Self Relations Questionnaire and the Short Form 36 (SF-36), patients completed questionnaires preoperatively and at 6, 12, and 24 months postoperatively. Mean scores were determined by repeated measures analyses of variance F tests., Results: One hundred seventy-five patients were surveyed before bariatric surgery, with noted declines in survey completion at 6, 12, and 24 months. Appearance Evaluation scores improved significantly at all intervals (P = 0.0033), as did Body Area Satisfaction Scale and Appearance Orientation scores (P = 0.0079 and P = 0.044, respectively). While Overweight Preoccupation and Self-Classified Weight scores decreased over time, only the latter was significant (P < 0.0001). The composite SF-36 score for patients awaiting bariatric surgery (54.1%) with postoperative scores at 6 (67.6%,), 12 (at 74.0%), and 24 (76.7%) months being significantly higher (P < 0.0001). The body contouring group consisted of 41 patients who primarily had lower body procedures, with 31 patients surveyed at 6 months and 27 patients at 12 months. For this cohort, Appearance Evaluation and Body Area Satisfaction Scale scores both improved significantly (P = 0.0001 and P = 0.0005, respectively) whereas Appearance Orientation scores declined significantly (P = 0.0055). Both Overweight Preoccupation and Self-Classified Weight scores decreased with only the latter being statistically significant (P = 0.0286). Postoperative SF-36 scores at 6 (72.9%) and 12 (64.5%) months were no different than patients awaiting body contouring (71.3%)., Conclusions: Using 2 validated survey instruments, we show that patients undergoing bariatric surgery have improvements in body image and quality of life. Subsequent postbariatric body contouring surgery results in further improvements in body image. Our findings provide measurable evidence for the value of body contouring after significant weight loss, which may favor greater insurance coverage for this patient population.

A resting mean pulmonary artery pressure (mPAP) of 21-24 mmHg is above the upper limit of normal but does not reach criteria for the diagnosis of pulmonary hypertension (PH). We sought to determine whether an mPAP of 21-24 mmHg is associated with an increased risk of developing an abnormal pulmonary vascular response during exercise.Consecutive patients (n=290) with resting mPAP <25 mmHg who underwent invasive exercise haemodynamics were analysed. Risk factors for pulmonary vascular disease or left heart disease were present in 63.4% and 43.8% of subjects. An abnormal pulmonary vascular response (or exercise PH) was defined by mPAP >30 mmHg and total pulmonary vascular resistance >3 WU at maximal exercise.Exercise PH occurred in 74 (86.0%) out of 86 versus 96 (47.1%) out of 204 in the mPAP of 21-24 mmHg and mPAP <21 mmHg groups, respectively (OR 6.9, 95% CI: 3.6-13.6; p<0.0001). Patients with mPAP of 21-24 mmHg had lower 6-min walk distance (p=0.002) and higher New York Heart Association functional class status (p=0.03). Decreasing levels of mPAP were associated with a lower prevalence of exercise PH, which occurred in 60.3%, 38.7% and 7.7% of patients with mPAP of 17-20, 13-16 and <13 mmHg, respectively.In an at-risk population, a resting mPAP between 21-24 mmHg is closely associated with exercise PH together with worse functional capacity., (Copyright ©ERS 2016.)

After endovascular aortic repair (EVAR), the deterioration in long-term renal function is probably multifactorial. Preoperative renal failure is an independent risk factor. Postoperative renal dysfunction can be associated with inadvertent renal artery occlusion, renal artery complications as stenosis, plaque dislodgement, or dissection. Ischemic nephropathy can accelerate hypertension and circulatory congestion. We report a case of coverage of the renal arteries symptomatic with flash pulmonary edema and renal failure 15 months after EVAR, suggesting a delayed endograft migration. The patient had complete resolution of symptoms and renal function after renal artery stenting with placement between endograft and aneurysm to the left renal artery., (© 2015 International Society for Hemodialysis.)