Nutritional deficiencies such as iron, vitamin B12 and folate are recognized as etiologies for several cytopenias; although copper’s role in multiple metabolic enzymes is well-established, copper deficiency is often overlooked as a contributing entity. Frequently diagnosis is delayed, patients may undergo bone marrow investigations with findings overlapping a myelodysplastic process, which can lead to further testing and treatment considerations including hematopoietic stem cell transplant referral. We present a case of a young boy with cystic fibrosis with biliary dysplasia corrected with hepato-portoenterostomy and distal intestinal obstruction syndrome resulting in jejunal resection, with severe anemia and thrombocytopenia requiring transfusion support. Initial evaluation had been unremarkable, ongoing pancytopenia prompted bone marrow studies, which revealed vacuolated granulocytic and erythroid precursors and ring sideroblasts, suggestive of copper deficiency. Serum copper and ceruloplasmin were consistent with severe deficiency, attributed to insufficient absorption intestinal resection, chronic parenteral nutrition and prior zinc supplementation. Following enteral copper supplementation, anemia, leukopenia and thrombocytopenia significantly improved, however upon cessation, counts again worsened and has since been maintained on daily copper supplementation without further transfusion needs. Our experience exemplifies the importance of early consideration for copper deficiency in children with cytopenias, especially within context of intestinal malabsorption or inadequate nutritional intake which often occurs in children with cystic fibrosis.
Habitat protection, by itself, is not sufficient to conserve range-restricted species with disjunct populations. Indeed, it becomes critical to characterize gene flow among the populations and factors that influence functional connectivity in order to design effective conservation programs for such species. In this study, we genotyped 314 individuals of Ivesia webberi, a United States federally threatened Great Basin Desert perennial forb using six microsatellite loci, to estimate genetic diversity and population genetic structure, as well as rates and direction of gene flow among 16 extant I. webberi populations. We assessed the effects of Euclidean distance, landscape features, and ecological dissimilarity on the genetic structure of the sampled populations, while also testing for a relationship between I. webberi genetic diversity and diversity in the vegetative communities. The results show low levels of genetic diversity overall (He = 0.200–0.441; Ho = 0.192–0.605) and high genetic differentiation among populations. Genetic diversity was structured along a geographic gradient, congruent with patterns of isolation by distance. Populations near the species’ range core have relatively high genetic diversity, supporting a central-marginal pattern, while peripheral populations have lower genetic diversity, significantly higher genetic distances, higher relatedness, and evidence of genetic bottlenecks. Genotype cluster admixture results support a predominant west to east gene flow pattern for populations near the species’ range center, as well as smaller genotype clusters with a narrow north to south distribution and little admixture, suggesting that dispersal direction and distance vary on the landscape. Pairwise genetic distance strongly correlates with actual evapotranspiration and precipitation, indicating a role for isolation by environment, which the observed phenological mismatches among the populations also support. The significant correlation between pairwise genetic distance and dissimilarity in the soil seed bank suggest that annual regeneration of the floristic communities contributes to the maintenance of genetic diversity in I. webberi.
Objective: To compare the host and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold to the response to PP mesh in an animal model of vaginal POP surgery. Design: A study employing a sheep model Setting: KU Leuven Center for Surgical Technologies Population: 14 parous female Mule sheep Methods: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical protocol. Main outcome measures: Gross necropsy, histological and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Results: Gross necropsy revealed no implant related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm (P=0.019)) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh (0.99 ± 0.78 SEM, score 0-4) at 180-days. Conclusions: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load bearing capacity. If these results are also observed at longer follow-up, a clinical study for vaginal POP surgery may be warranted to demonstrate efficacy. Key words: Pelvic organ prolapse, vaginal surgery, Poly-4-hydroxybutyrate, degradable scaffold, host response, biomechanics.
The effects of the discharge of wastewater treatment plants (WWTP) on the status of rivers have most commonly been focused on water quality. A very limited number of works have characterised the ability of treatment plants to modify flow patterns in the receiving rivers. This paper presents a methodology for the assessment of the hydrologic alteration caused by WWTP discharges, over a two-fold sequence. The first phase comprises the application of indicators derived from accessible data and informative of the capacity of treatment plants to produce significant flow alterations. The second phase, which may only be carried out when flow data in the receiving river is available, is based on the indicators of hydrologic alteration provided by the free software IAHRIS (6 indicators) and IHA (2 indicators), and on a new indicator proposed in this paper to obtain information of flow alteration at seasonal and monthly time scales. The procedure suggested in this work is applied to the Manzanares River (Central Spain), allowing the quantification of the flow alteration generated by the 12 WWTP which give service to Madrid city (3.8 million inhabitants): Large increases of annual water volumes (from 108 hm3 to 410 hm3); at a monthly scale (increase from 246% to 1516%); variability in flow decreases in wet years by up to 47% and increases in dry years by up to 380%; seasonal patterns is altered within an altered regime. Results of the analysis show: (i) the ability of the proposed methodology to characterise the modification of flow patterns due to WWTP discharges; (ii) the importance of assessing such changes when evaluating the environmental impact of treatment plants; (iii) the importance of designing preventive and mitigation measures which maintain the ecological integrity of river ecosystems in the receiving channels.
We evaluated whether evolution is faster at ecotones as niche shifts may be needed to persist under unstable environment. We mapped diet evolution along the evolutionary history of 350 sigmodontine species. Mapping was used in three new tip-based metrics of trait evolution–Transition Rates, Stasis Time, and Last Transition Time–which were spatialized at the assemblage level (aTR, aST, aTL). Assemblages were obtained by superimposing range maps on points located at core and ecotone of the 91 South American ecoregions. Using Linear Mixed Models, we tested whether ecotones have species with more changes from the ancestral diet (higher aTR), have maintained the current diet for a shorter time (lower aST) and have more recent transitions to the current diet (lower aLT) than cores. We found higher aTR, aST and aLT at ecotones than at cores. Although ecotones are more heterogeneous, both environmentally and in relation to selection pressures they exert on organisms, ecotone species change little from the ancestral diet as generalist habits are necessary toward feeding in ephemeral environments. The need to incorporate phylogenetic uncertainty in tip-based metrics was evident from large uncertainty detected. Our study integrates ecology and evolution by analyzing how fast trait evolution is across space.
Immune modulation is a key therapeutic tool for allergic diseases and asthma. It can be achieved in an antigen-specific way via allergen immunotherapy (AIT) or in endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: IgE, IL-5 and IL-4/IL-13. COVID-19 vaccine provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. It works as well through immune modulation. Thus, as there is an obvious interference between these treatment modalities recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) gathered an outstanding expert panel under its Research and Outreach Committee (ROC). This expert panel was called to evaluate the evidence and formulate recommendation on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.
Forestier disease is a condition characterized by calcification and ossification of ligaments and entheses. It's prevalence is expected to rise as air is related to older age and metabolic syndrome. The clinical relevance is beyond unstable spinal fractures to involvement of the cardiovascular, respiratory and gastrointestinal systems.
Microbial fuel cell (MFC) is an evolving technology for anaerobic bioenergy generation using electrodes and organic wastewater as a feedstock for catabolic activities of electrogenic bacteria and subsequent electricity generation. The search for suitable inexpensive electrode materials remains the leading interest of researchers in this field. The work here focused on comparative bioelectricity generation from HTC process water (pH = 5.99) and treated–biogas digestate (pH = 7.97) using locally developed corncob pyrochar electrodes and graphite in dual-chambered microbial fuel cells (MFC). The electrodes used in this study were graphite rod (non-porous and very low surface area), KOH–activated corncob pyrochar (KAC) of BET surface area, 1626 m2 g-1 and steam activated corncob pyrochar (SAC) with 485.8 m2 g-1. The highest power outputs achieved were 323.8 µW and 316.8 µW from HTC process water with SAC and KAC electrodes respectively at an external load of 47 Ω. The initial COD (48780 mg L-1), DOC (4000 mg L-1), and TNb (5600 mg L-1) of the biogas digestate decreased significantly to 36405, 3610 and 4300 mg L-1 respectively in the MFC with KOH-activated corncob pyrochar electrodes. The MFC operated with KAC electrode and treated biogas digestate was the most efficient having Coulombic efficiency of 75 % in a comparatively shorter residence time of MFC operation than the MFC with SAC electrode which had a lower Coulombic efficiency of 64 %.
Background Silent aspirations are frequent in children with neurological impairment. They dramatically increase the risk for acute and chronic respiratory insufficiencies leading to high morbidity and mortality. Laryngeal sensitivity deficits have been linked to aspirations in adults and are a suspected cause for dysphagia in children. In a similar neurological circuit as swallowing, laryngeal receptors trigger coughing as a protective airway reflex. The aim of this study was to examine the association between reduced laryngeal sensitivity, aspiration and coughing in neurologically impaired children. Design and Methods In a retrospective study, 110 children with suspected dysphagia who received a clinical evaluation of swallowing and a flexible endoscopic evaluation of swallowing (FEES) between 2013 and 2019 in the children’s university clinic Düsseldorf were analyzed. Laryngeal sensitivity was tested by the endoscopic touch method. Fifty-four patients (49.1%) had neurological impairments, 56 patients (5.9%) had no or other comorbidities and served as a control cohort. Associations were computed using χ2-test. Results Children with neurological impairment suffered from laryngeal sensory deficit significantly more often and seemed to cough less frequently than children with no or other comorbidities. Reduced laryngeal sensitivity could not be correlated to less coughing. Coughing acted as a predictor of aspiration only in the neurologically impaired group of children with reduced laryngeal sensitivity. Conclusion Reduced laryngeal sensitivity is a potential cause of silent aspirations in children with neurological impairment. However, reduced laryngeal sensitivity did not lead to significantly less coughing which might be due to a lack of discrimination between different levels of sensitivity deficits by the endoscopic touch.
Liver fibrosis induced by chronic hepatic injury remains as a major cause of morbidity and mortality worldwide. Identification of susceptibility/prognosis factors and new therapeutic tools for treating hepatic fibrotic disorders of various etiologies are urgent medical needs. Cortistatin is a neuropeptide with potent anti-inflammatory and anti-fibrotic activities in lung that binds to receptors that are expressed in liver fibroblasts and hepatic stellate cells. Here, we evaluated the capacity of cortistatin to regulate liver fibrosis. We initially found that hepatic expression of cortistatin inversely correlated with liver fibrosis grade in mice and humans with hepatic disorders. Cortistatin-deficient mice showed exacerbated signs of liver damage and fibrosis and increased mortality rates when challenged to hepatotoxic and cholestatic injury. Compared to wild-type mice, non-parenchymal liver cells isolated from cortistatin-deficient mice showed increased presence of cells with activated myofibroblast phenotypes and a differential genetic signature that is indicative of activated hepatic stellate cells and periportal fibroblasts and of myofibroblasts with active contractile apparatus. Cortistatin treatment reversed in vivo and in vitro these exaggerated fibrogenic phenotypes and protected from progression to severe liver fibrosis in response to hepatic injury. In conclusion, we identify cortistatin as an endogenous molecular break of liver fibrosis and its deficiency as a potential poor-prognosis marker for chronic hepatic disorders that course with fibrosis. Cortistatin-based therapies emerge as attractive strategies for ameliorating severe hepatic fibrosis.
Title PageTitle : Pancytopenia in a child with cystic fibrosis and severe copper deficiency: Insight from bone marrow evaluationAuthors : Maggie D. Seblani1,2; Susanna A. McColley2,3,4; Shunyou Gong5; Lee M. Bass2,6; Sherif M. Badawy1,2Affiliations : 1 Division of Hematology, Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 2 Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3 Division of Pulmonary and Sleep Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 4 Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA; 5 Division of Pediatric Pathology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL; 6 Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL.Correspondence: Sherif M. Badawy, MD, MS, MBBCh, 225 E. Chicago Ave., Box #30, Chicago, IL, 60611, office: 312-227-4836, fax: 312-227-9376, e-mail: email@example.comWord count: 498Number of Tables, Figures, and Supplemental files : 1Running title: Bone marrow findings with severe copper deficiencyKeywords: pancytopenia, anemia, leucopenia, neutropenia, thrombocytopenia, copper deficiency, ring sideroblasts, copper supplement, cystic fibrosis, malabsorptionConflict of Interest: Author has no conflicts of interest to disclose.
Introduction/Objectives: We evaluated the length of time immunocompromised children (ICC) remain positive for SARS-CoV-2, identified factors associated with viral persistence and determined cycle threshold (CT) values of children with viral persistence as a surrogate of viral load. Methods: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary, secondary or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first-of-two consecutive negative SARS-CoV-2 Polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV Real-Time RT-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank-sum tests were used to compare outcomes between groups. Results: Ninety-one children met inclusion criteria. Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% were white, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had >1 sample available for repeat testing, and 5/7 (71%) children had initial CT values of <30, (moderate to high viral load); 4 children had CT values of <30 3-4 weeks later, suggesting persistent moderate to high viral loads. Conclusions: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.
Arbuscular mycorrhizal fungi (AMF), the mutualistic symbionts with most crops, constitute a research system of human-associated fungi whose relative simplicity and synchrony are conducive to experimental ecology. However, little is known about the shifts in adaptive strategies of sorghum associated AMFs where strong AMF succession replaces initially ruderal species with competitive ones and where the strongest plant response to drought is to manage these AMF. First, we hypothesize that, when irrigation is stopped to mimic drought, competitive AMF species should be replaced by AMF species tolerant to drought stress. We then, for the first time, correlate AMF abundance and host plant transcription to test two novel hypotheses about the mechanisms behind the shift from ruderal to competitive AMF. Surprisingly, despite imposing drought stress, we found no stress tolerant AMF. Remarkably, we found strong and differential correlation between the successional shift from ruderal to competitive AMF and sorghum genes whose products (i) produce and release strigolactone signals, (ii) perceive mycorrhizal-lipochitinoligosaccharide (Myc-LCO) signals, (iii) provide plant lipid and sugar to AMF and, (iv) import minerals and water provided by AMF. These novel insights into host gene expression and succession of AMF show adaptive strategies evolved by AMF and their hosts and provide a rationale for selecting AMF to reduce inputs and maximize yield in commercial agriculture. Future research opportunities include testing the specifics and generality of our hypotheses by employing genetically modified host plants, and exploring additional genes underlying the adaptive strategies in natural succession.
It is a rare event that a patient suspected to have a subglottic stenosis actually has a foreign body bronchus. We report a suspected case of subglottic stenosis secondary to partial hanging and prolonged intubation. However, surprisingly the rigid bronchoscopy revealed a betel nut at the level of carina.
Background: The effectiveness of montelukast for wheezing in young children is not clear. We aimed to evaluate whether the use of montelukast in the treatment of wheezing affects the number of attacks in children aged 1 to 6 years. Methods: This is a single center study. It was conducted between August 2019 – 2020. Children with aged 0-6 years old with a wheezing complaint who applied to the pediatric allergy and immunology outpatient clinic were included in the study. Modified asthma predictive index of the patients were evaluated. It was classified as episodic viral wheezing (EVW) or multiple trigger wheezing (MTW) based on the type of wheezing. Montelukast treatment was started and the number of attacks was checked. Results: The total of 141 children who applied with wheezing complaints were included in the study. The majority of the patients were boys (n=99). The mean age of the children was 4.2 ± 1.5 years. The median number of attacks before treatment was 2 (2-3). In 2.8% of the patients, eczema, in 12.8% of them, rhinitis and in 26.7% of them, elevated eosinophils were detected. IgE levels were 148.25 ± 279.20 IU/mL. According to the number of attacks before treatment, there was a significant decrease in the number of attacks in the control (p <0.001). Conclusion: In this study, montelukast has been shown to reduce the number of EVW attacks and we believe montelukast may be a potential treatment option for EVW in preschool children.
Evaluation of Ventilator-Associated Tracheitis in Children with Pre-Existing Tracheostomies: Organisms and Empiric Coverage Objectives: This study aims to describe the outcomes, microbiome, and empiric antimicrobial coverage of ventilator associated tracheitis (VAT) in pediatric patients with pre-existing tracheostomies. Patients and Methods: This is a retrospective chart review of pediatric patients with pre-existing tracheostomies admitted to the Children’s Hospital of Georgia for initial inpatient treatment for VAT between January 1, 2007 and February 21, 2021. Patients were evaluated for incidence of ventilator associated pneumonia (VAP), tracheostomy culture results, and antibiotic choice. Results: Thirty-nine patients were included. Across all patients evaluated with pre-existing tracheostomies, 60% developed VAT. There was no difference in the development in VAP between shorter and longer treatment durations (0 vs 1, p = 1). Patients who developed Pseudomonas aeruginosa VAT were likely to have a previous culture of P. aeruginosa (p = 0.003), have a tracheostomy for longer (p = 0.011), and be older than 1 year of age (p = 0.0002). MRSA VAT was associated with a previous culture growing MRSA (p= 0.0042). Conclusions: VAT incidence was higher than what was shown in pediatric patients without pre-existing tracheostomies but VAP incidence was lower and there was no difference between treatment groups. VAT should be treated based on previous cultures and Pseudomonas aeruginosa should be considered as a causative organism.
Reports of early and catastrophic acute structural valve deterioration (SVD) in Trifecta valves (Abbott, St Paul, MN, USA) with multiple leaflet detachment are rare. We encountered two cases of early SVD in Trifecta valves with tears on two leaflets. Both cases presented with acute heart failure because of aortic insufficiency and underwent redo aortic valve replacement; one patient died due to multiple organ failure caused by cardiogenic shock. Durability issues with valves necessitate long-term vigilance in aortic valve replacement patients.