Gum Arabic assisted the biomass synthesis of bimetallic silver copper oxide nanoparticles using gamma-rays for improving bacterial and viral wound healing: Promising antimicrobial activity against foot and mouth disease.

In this work, gamma irradiation was used to create bimetallic silver­copper oxide nanoparticles (Ag-CuO NPs) in an ecologically acceptable way using gum Arabic (GA) polymer as a capping and reducing agent. Bimetallic Ag-CuO NPs were investigated through UV-Vis. spectroscopy, HR-TEM, SEM, DLS, and XRD examinations. The potency of antimicrobial and antibiofilm activities against a few bacterial isolates and Candida sp. had been investigated. Clinical investigations of 30 cows and 20 buffaloes from different sites in Egypt's Sharkia governorate found ulcerative lesions on the mouth and interdigital region. The cytotoxic assay of the generated NPs on BHK-21 was examined. The bimetallic Ag-CuO NPs had an average diameter of 25.58 nm, and the HR-TEM results showed that they were spherical. According to our results, Ag-CuO NPs exhibited the highest antibacterial efficacy against S. aureus (26.5 mm ZOI), K. pneumoniae (26.0 mm ZOI), and C. albicans (28.5 mm ZOI). The growth of biofilms was also successfully inhibited through the application of Ag-CuO NPs by 88.12 % against S. aureus, 87.08 % against C. albicans, and 74.0 % against B. subtilis. The ulcers on the mouth and foot of diseased animals healed in 4-5 days and 1 week, respectively, following topical application of bimetallic Ag-CuO NPs. The results examined the potential protective effects of a dosage of 3.57 µg/mL on cells before viral infection (cell control). According to our research, bimetallic Ag-CuO NPs limit the development of the virus that causes foot-and-mouth disease (FMD). The reduction of a specific FMD virus's cytopathic impact (CPE) on cell development represented the inhibitory effect when compared to identical circumstances without pretreatment with bimetallic Ag-CuO NPs. Their remarkable antibacterial properties at low concentration and continued-phase stability suggest that they may find widespread use in a variety of pharmacological and biological applications, especially in the wound-healing process.

Promising sensors for pharmaceutical pollutant adsorption using Clar's goblet-based 2D membranes.

This study focuses on the design of new 2D membranes from connected Clar's Goblet as a potential sensor for pharmaceutical pollutants, specifically the painkiller drugs aspirin, paracetamol, ibuprofen, and diclofenac. The electronic, optical, and interaction properties are investigated using density functional theory calculations. The Clar's Goblet membranes (CGMs) that were chosen are semiconductors with an energy gap of around 1.5 eV, according to energy gap calculations and density of states. Molecular electrostatic potential (ESP) analysis shows that CGMs have electrophilic and nucleophilic sites, suggesting their suitability for interacting with pharmaceutical pollutants. The adsorption energies confirm the chemical adsorption of pharmaceutical pollutants with diclofenac showing the strongest adsorption. The UV-Vis absorption spectra of CGMs-drug complexes are analyzed, revealing a redshift compared to the absorption spectrum of CGMs alone, confirming the adsorption of these drugs. Further analysis using hole/electron examinations indicates that the type of excitation is local excitation rather than charge transfer excitation. This study quantitatively characterized hole and electron distribution in excited states using various indices. The analysis revealed local excitation transitions and significant charge transfer between the CGMs molecule and pharmaceutical pollutants. Additionally, non-covalent interaction analysis indicates the presence of van der Waals interactions, highlighting the adsorption behavior of the drugs. These results demonstrate the potential of CGMs as a highly sensitive sensor for pharmaceutical pollutants.

Exploring the Potential of Chemically Modified Graphyne Nanodots as an Efficient Adsorbent and Sensitive Detector of Environmental Contaminants: A First Principles Study.

In this study, we investigated the reactivity of γ-graphyne (Gp) and its derivatives, Gp-CH3, Gp-COOH, Gp-CN, Gp-NO2, and Gp-SOH, for the removal of toxic heavy metal ions (Hg+ 2, Pb+ 2, and Cd+ 2) from wastewater. From the analysis of the optimized structures, it was observed that all the compounds exhibited planar geometry. The dihedral angles (C9-C2-C1-C6 and C9-C2-C1-C6) were approximately 180.00°, indicating planarity in all molecular arrangements. To understand the electronic properties of the compounds, the HOMO (EH) and LUMO (EL) energies were calculated, and their energy gaps (Eg) were determined. The EH and EL values ranged between - 6.502 and - 8.192 eV and - 1.864 and - 3.773 eV, respectively, for all the compounds. Comparing the EH values, Gp-NO2 exhibited the most stable HOMO, while Gp-CH3 had the least stable structure. In terms of EL values, Gp-NO2 had the most stable LUMO, while Gp-CH3 was the least stable. The Eg values followed the order: Gp-NO2 < Gp-COOH < Gp-CN < Gp-SOH < Gp-CH3 < Gp, with Gp-NO2 (4.41 eV) having the smallest energy gap. The density of states (DOS) analysis showed that the shape and functional group modifications affected the energy levels. Functionalization with electron-withdrawing (CN, NO2, COOH, SOH) or electron-donating (CH3) groups reduced the energy gap. To specifically target the removal of heavy metal ions, the Gp-NO2 ligand was selected for its high binding energy. Complexes of Gp-NO2-Cd, Gp-NO2-Hg, and Gp-NO2-Pb were optimized, and their properties were analyzed. The complexes were found to be planar, with metal-ligand bond distances within the range of 2.092→3.442 Å. The Gp-NO2-Pb complex exhibited the shortest bond length, indicating a stronger interaction due to the smaller size of Pb+ 2. The computed adsorption energy values (Eads) indicated the stability of the complexes, with values ranging from - 0.035 to -4.199 eV. Non-covalent interaction (NCI) analysis was employed to investigate intermolecular interactions in Gp-NO2 complexes. The analysis revealed distinct patterns of attractive and repulsive interactions, providing valuable insights into the binding preferences and steric effects of heavy metals.

Shedding Light on the Role of ERAP1 in Axial Spondyloarthritis.

Spondyloarthritis (SpA) is a multifactorial chronic inflammatory disease affecting the axial skeleton (axSpA) and/or peripheral joints (p-SpA) and entheses. The disease's pathogenesis depends on genetic, immunological, mechanical, and environmental factors. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme that shapes the peptide repertoire presented by major histocompatibility complex (MHC) class I molecules. Genome-wide association studies (GWAS) have identified different single nucleotide polymorphisms (SNPs) in ERAP1 that are associated with several autoimmune diseases, including axSpA. Therefore, a deeper understanding of the ERAP1 role in axSpA could make it a potential therapeutic target for this disease and offer greater insight into its impact on the immune system. Here, we review the biological functions and structure of ERAP1, discuss ERAP1 polymorphisms and their association with axSpA, highlight the interaction between ERAP1 and human leukocyte antigen (HLA)-B27, and review the association between ERAP1 SNPs and axSpA clinical parameters.

Electronic and optical properties of chemically modified 2D GaAs nanoribbons.

We employed density functional theory calculations to investigate the electronic and optical characteristics of finite GaAs nanoribbons (NRs). Our study encompasses chemical alterations including doping, functionalization, and complete passivation, aimed at tailoring NR properties. The structural stability of these NRs was affirmed by detecting real vibrational frequencies in infrared spectra, indicating dynamical stability. Positive binding energies further corroborated the robust formation of NRs. Analysis of doped GaAs nanoribbons revealed a diverse range of energy gaps (approximately 2.672 to 5.132 eV). The introduction of F atoms through passivation extended the gap to 5.132 eV, while Cu atoms introduced via edge doping reduced it to 2.672 eV. A density of states analysis indicated that As atom orbitals primarily contributed to occupied molecular orbitals, while Ga atom orbitals significantly influenced unoccupied states. This suggested As atoms as electron donors and Ga atoms as electron acceptors in potential interactions. We investigated excited-state electron-hole interactions through various indices, including electron-hole overlap and charge-transfer length. These insights enriched our understanding of these interactions. Notably, UV-Vis absorption spectra exhibited intriguing phenomena. Doping with Te, Cu, W, and Mo induced redshifts, while functionalization induced red/blue shifts in GaAs-34NR spectra. Passivation, functionalization, and doping collectively enhanced electrical conductivity, highlighting the potential for improving material properties. Among the compounds studied, GaAs-34NR-edg-Cu demonstrated the highest electrical conductivity, while GaAs-34NR displayed the lowest. In summary, our comprehensive investigation offers valuable insights into customizing GaAs nanoribbon characteristics, with promising implications for nanoelectronics and optoelectronics applications.

Bioinductive Collagen Implant Augmentation for Myotendinous Achilles Rupture in a Teenage Competitive Gymnast: A Case Report.

CASE: A 16-year-old female competitive gymnast presented to our orthopaedic clinic with an acute Achilles tendon rupture at the myotendinous junction. Direct end-to-end repair was performed and augmented with a bioinductive collagen patch. The patient had increased tendon thickness at 6 months postoperatively, as well as significant improvements in strength and range of motion at 12 months. CONCLUSION: Bioinductive collagen patch augmentation of Achilles tendon repair may be a useful adjunct for myotendinous junction Achilles ruptures, particularly in high-demand patients including competitive gymnasts.

Chemically modified covalent organic frameworks for a healthy and sustainable environment: First-principles study.

Pure water is a key element for a sustainable and healthy environment of human inhabitation. Since major sources of water contamination are industrially generated heavy metal cations there is great demand for efficient methods of their treatment. Here, using density functional theory, we investigate the covalent organic framework's electronic and optical properties and their interaction with the most dangerous heavy metal pollutants, namely Hg+2, Pb+2, and Cd+2. We consider biphenyl boroxine covalent organic frameworks before and after chemical modification with CN, COOH, NH2, and NO2 groups. In addition to the molecular geometries, such parameters as the dipole moment, chemical potential, electronegativity, chemical hardness, and binding energy are calculated. It is found that CN, COOH, and NO2 functional groups are favorable for intermolecular bonding with harmful transition metals. The functionalization with the mentioned groups reduces the band gap of the pristine covalent organic frameworks and increases their reactivity. As a result, strong complexes with Cd+2, Hg+2, and Pb+2 can form, which, as follows from our calculations, can be detected by the red shift in their optical absorption spectra.

Assessment of plasmablast cells in immune thrombocytopenic purpura in children.

Primary immune thrombocytopenic purpura (ITP) is an autoimmune disorder with platelet destruction due to B- and T-cell dysregulation and antiplatelet autoantibodies production. Flow cytometry can be used to further characterize the B- and T-cell compartments involved in platelet destruction. This case-control study was to enumerate plasmablast cells in pediatric ITP patients and to correlate their levels with disease course. This study included 30 ITP patients and 10 controls. Identification and enumeration of Plasmablast were done by multicolor flow cytometry using specific antibody panels (CD19, CD27 & CD38) and sequential gating using FACSCanto flow cytometer and FlowJo software. We found that lymphocytes subpopulation in ITP patients and controls revealed increase in frequency of CD19 (B lymphocytes) in acute, persistent, and chronic ITP patients in comparison with controls (p < 0.001, 0.023, 0.001) respectively. Plasmablast cells could play a role in the pathogenesis of ITP and might guide therapy in ITP patients in the future.

Prediction of motor recovery after ischemic stroke: Clinical and diffusion tensor imaging study.

BACKGROUND: The severity of stroke-induced disruption to the corticospinal tract (CST) would be predictable to affect motor outcome. Diffusion tensor imaging (DTI) is a noninvasive technique that can be applied to assess the structural integrity of the CST. AIM OF THE WORK: To assess the value of DTI in patients early presenting with acute ischemic stroke as a prognostic modality to predict the clinical outcome PATIENTS AND METHODS: Thirty-four patients with acute ischemic stroke underwent clinical assessment using the National Institutes of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Medical Research Council (MRC) score, Morticity Index (MI), and DTI to detect the degree of reduction of fractional anisotropy (FA), and pattern of CST at baseline and after 6 months follow up. Seventeen age, sex matched controls underwent DTI assessment. RESULTS: The stroke patients showed a significant reduction in the baseline FA values of the CSTs on the affected sides compared to the contralateral sides and controls. Moreover, they showed lower mean baseline FA lesion side and FA ratio(rFA) compared to follow up. The patients with high baseline FA, rFA showed good recovery response with cut off values of 0.483, 0.948 respectively. There was a significant negative correlation between baseline FA on the lesion side, rFA and follow up NIHSS, and MRS scores and they had a significant positive correlation with follow up MI scores. CONCLUSION: Patients with higher baseline FA, rFA values were correlated with better motor recovery, and could predict the motor recovery in ischemic stroke patients.

COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients.

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1ß, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.

Safety and immunogenicity evaluation of inactivated whole-virus-SARS-COV-2 as emerging vaccine development in Egypt.

BACKGROUND: Current worldwide pandemic coronavirus disease 2019 (COVID-19) with high numbers of mortality rates and huge economic problems require an urgent demand for safe and effective vaccine development. Inactivated SARS-CoV2 vaccine with alum. Hydroxide can play an important role in reducing the impacts of the COVID-19 pandemic. In this study, vaccine efficacy was evaluated through the detection of the neutralizing antibodies that protect mice from challenge with SARS-CoV 2 3 weeks after the second dose. We conclude that the vaccine described here has safety and desirable properties, and our data support further development and plans for clinical trials. METHODS: Characterized SARS-COV-2 strain, severe acute respiratory syndrome coronavirus 2 isolates (SARS-CoV-2/human/EGY/Egy-SERVAC/2020) with accession numbers; MT981440; MT981439; MT981441; MT974071; MT974069; and MW250352 at GenBank were isolated from Egyptian patients SARS-CoV-2-positive. Development of inactivated vaccine was carried out in a BSL-3 facilities and the immunogenicity was determined in mice at two doses (55 and 100 µg per dose). RESULTS: The distinct cytopathic effect induced by SARS-COV-2 propagation on Vero cell monolayers and the viral particles were identified as Coronaviridae by transmission electron microscopy and RT-PCR on infected cells cultures. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless of the dose concentration, with excellent safety profiles and no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by the wild virus challenge of the vaccinated mice and viral replication detection in lung tissues. CONCLUSIONS: Vaccinated mice recorded complete protection from challenge infection via inhibition of SARS-COV-2 replication in the lung tissues of mice following virus challenge, regardless of the level of serum neutralizing antibodies. This finding will support future trials for the evaluation of an applicable SARS-CoV-2 vaccine candidate.

Physiologic Improvement in Respiratory Acidosis Using Extracorporeal Co2 Removal With Hemolung Respiratory Assist System in the Management of Severe Respiratory Failure From Coronavirus Disease 2019.

OBJECTIVES: About 15% of hospitalized coronavirus disease 2019 patients require ICU admission, and most (80%) of these require invasive mechanical ventilation. Lung-protective ventilation in coronavirus disease 2019 acute respiratory failure may result in severe respiratory acidosis without significant hypoxemia. Low-flow extracorporeal Co2 removal can facilitate lung-protective ventilation and avoid the adverse effects of severe respiratory acidosis. The objective was to evaluate the efficacy of extracorporeal Co2 removal using the Hemolung Respiratory Assist System in correcting severe respiratory acidosis in mechanically ventilated coronavirus disease 2019 patients with severe acute respiratory failure. DESIGN: Retrospective cohort analysis of patients with coronavirus disease 2019 mechanically ventilated with severe hypercapnia and respiratory acidosis and treated with low-flow extracorporeal Co2 removal. SETTING: Eight tertiary ICUs in the United States. PATIENTS: Adult patients supported with the Hemolung Respiratory Assist System from March 1, to September 30, 2020. INTERVENTIONS: Extracorporeal Co2 removal with Hemolung Respiratory Assist System under a Food and Drug Administration emergency use authorization for coronavirus disease 2019. MEASUREMENTS AND MAIN RESULTS: The primary outcome was improvement in pH and Paco2 from baseline. Secondary outcomes included survival to decannulation, mortality, time on ventilator, and adverse events. Thirty-one patients were treated with Hemolung Respiratory Assist System with significant improvement in pH and Pco2 in this cohort. Two patients experienced complications that prevented treatment. Of the 29 treated patients, 58% survived to 48 hours post treatment and 38% to hospital discharge. No difference in age or comorbidities were noted between survivors and nonsurvivors. There was significant improvement in pH (7.24 ± 0.12 to 7.35 ± 0.07; p < 0.0001) and Paco2 (79 ± 23 to 58 ± 14; p < 0.0001) from baseline to 24 hours. CONCLUSIONS: In this retrospective case series of 29 patients, we have demonstrated efficacy of extracorporeal Co2 removal using the Hemolung Respiratory Assist System to improve respiratory acidosis in patients with severe hypercapnic respiratory failure due to coronavirus disease 2019.

Improving the diagnosis of bovine tuberculosis using gold nanoparticles conjugated with purified protein derivative: special regard to staphylococcal protein A and streptococcal protein G.

Different ancillary immunodiagnostic tests were traditionally-established for diagnosis of bovine tuberculosis (BTB) either cellular or humoral as tuberculin skin test (TST), gamma interferon (INF-γ), and indirect enzyme-linked immunosorbent assay (iELISA). These tests had been consumed more time and expensive, and needed sophisticated equipment. To dissolve these problems, serological diagnosis depending on humoral immunity is the aim of this work. Herein, slide-based agglutination test was chosen as a rapid and simple field test based on purified protein derivative (PPD) antigen in addition to some supplementation materials such as Staphylococcal protein A (SPA) and Streptococcal protein G (SPG) to improve detection of BTB antibody in serum samples. Gold nanoparticles (Au NPs) were synthesized by gamma ray, and after complete characterization, the synthesized Au NPs were spherical, small-sized, and stable without any impurities. Addition of such supplementation reagents for serodiagnosis of tuberculosis is of paramount important for the detection of serum antibodies against tuberculosis (TB) and it was considered an easily simple and possible way for improving TB diagnosis. In this work, 70 animals tested positive for TST as well as 20 animals tested negative for TST were used for the diagnosis of BTB depending on humoral immune response based on PPD slide agglutination test using reporter regents (SPA and/or SPG) either native or recombinant. The agglutination density was recorded and read in 4 degrees of positivity with scores ranging from negative (-) to very strong reaction (++++) occurred in different times of agglutination. Groups showed 100% positive reactivates employed in Exp. 1, 2, and 3 with differentiation of slide agglutination test density and was rated from moderate positivity (2+) to very strong (4+), with predominant positivity in density of (3+). Pink-colored intensity is associated with the strengthened reactions between PPD-conjugated Au NPs and serum antibody of each tested samples, which allows for visual rapid, simple, and effective attractive diagnosis of BTB. The specificity and sensitivity of the serological tests were characterized. TST offers the highest sensitivity (83.6%) among the other immunoassays, while the lowest specificity was recorded in TST (57.4%). SPA/SPG offers the best performance in term of combined sensitivity and specificity (performance index) of 175.4. Therefore, the development and uses of detection reagent (such as SPA and/or SPG) slide co-agglutination test (COAT), either native or recombinant (rSPA/SPG) for the detection of TB antibodies based on PPD antigen, as well as the uses of Au NPs rSPA/SPG as detection conjugate based on the same antigen, were also performed as a simple, rapid, sensitive, specific, eco-friendly, and low cost, which shows a great potential in field and lab diagnosis of BTB. So, high reduction in reagents that yields reactions similarly as traditional techniques was needed.

Myeloid-derived suppressor cells anticipate sustained treatment response in newly-diagnosed and persistent primary immune thrombocytopenia.

BACKGROUND: Myeloid-Derived Suppressor Cells (MDSCs) are used as markers for short-term immune thrombocytopenia (ITP) course. This study aimed to assess their reliability to predict the sustained treatment response within 6 months. METHODS: We tested the sensitivity and specificity of MDSCs and proposed cut-off MDSCs values to predict the prognosis in newly diagnosed ITP. We enrolled 80 adults with primary ITP; 50 newly diagnosed (group I), 30 chronic (group II), and 20 controls (group III). Flow cytometry was used for peripheral blood MDSCs estimation with correlation, sensitivity, and specificity of MDSCs to predict sustained treatment response. RESULTS: After 6 days and 6 months of treatment, MDSCs were significantly higher than pre-treatment in group I, (P < 0.001, P < 0.001). MDSCs were significantly higher in group I compared to groups II and III, (P < 0.001 for both). Cut-off values were 15.75% and >5.9% at 6 days and 6 months respectively. MDSCs sensitivity was 85.7% and 100% and specificity was 94.44% and 100% at 6 days and 6 months. CONCLUSIONS: MDSCs may constitute a reliable predictor for ITP initial and prolonged treatment response with good sensitivity and specificity. This may guide the use of a specific therapeutic agent as maintenance therapy or its replacement in practice.

Pharmacokinetic and Pharmacodynamic Profiling of Minocycline for Injection following a Single Infusion in Critically Ill Adults in a Phase IV Open-Label Multicenter Study (ACUMIN).

Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [fAUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of A. baumannii were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (fub) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with fub). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with A. baumannii infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.

Antibiotic Timing and Outcomes in Sepsis.

BACKGROUND: We evaluated the effect of time spent in the emergency department (ED) and process of care on mortality and length of hospital stay in patients with sepsis or septic shock. METHODS: An observational cohort study was conducted on 117 patients who came through the University of Louisville Hospital ED and subsequently were directly admitted to the intensive care unit (ICU). Variables of interest were time in the ED from triage to physical transport to the ICU, from triage to antibiotic(s) ordered, and from triage to antibiotic(s) administered. Expected mortality was calculated according to the University Health System Consortium Database. Primary and secondary outcomes were in-hospital death and hospital length of stay in days, respectively. RESULTS: We found no significant association between time in the ED and mortality between survivors and nonsurvivors (5.5 versus 5.7 hours, P = 0.804). After adjusting for expected mortality, a 22% increase in mortality risk was found for each hour delay from triage to antibiotic(s) ordered; a 15% increase in mortality risk was observed for each hour from triage to antibiotic(s) given. Both time from triage to antibiotic(s) ordered (hazard ratio [HR] = 0.8, P = 0.044) and time from triage to antibiotic(s) delivery (HR = 0.79, P = 0.0092) were independently associated with an increased hospital stay (HR = 0.79, P = 0.0092). CONCLUSION: Though no significant association between mortality and ED time was demonstrated, we observed a significant increase in mortality in septic patients with both delays in antibiotic(s) order and administration. Delay in care also resulted in increased hospital stays both overall and in the ICU.

Clinical significance of thymidine kinase in Egyptian children with acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, representing one-third of pediatric cancers. Thymidine kinase-1 (TK-1) is expressed in proliferating cells so elevated TK-1 indicates active tumor growth. OBJECTIVE: To study the clinical significance of TK-1 in children with ALL. PATIENTS AND METHODS: This study was carried out on 40 children with newly diagnosed ALL who were admitted to Oncology Unit, Pediatric department, Tanta University (26 males and 14 females) with their ages ranged from 4 to 10 years and 30 healthy children of matched age and sex as a control group. For all patients the following were done: Complete blood picture, bone marrow examination, immunophenotyping and TK-1 serum levels. RESULTS: Mean TK-1 level was significantly higher in patients at diagnosis than controls and significantly higher in patients with unfavorable outcome than patients with favorable outcome. Mean TK-1 level was significantly higher in patients in relapse than patients in remission and controls. No significant differences in mean TK-1 level between patients in remission and controls. There were statistically significant differences in disease free survival and overall survival between patients with favorable and unfavorable outcome. CONCLUSION: From this study we concluded that TK is a helpful marker in diagnosis and follow-up of patients with ALL. RECOMMENDATIONS: Thymidine kinase-1 should be routinely assessed at diagnosis and during follow-up in ALL patients for better diagnostic and prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patients-specific risk factors.

Volume-Based Feeding in the Critically Ill Patient.

INTRODUCTION: Critically ill patients placed on enteral nutrition (EN) are usually underfed. A volume-based feeding (VBF) protocol designed to adjust the infusion rate to make up for interruptions in delivery should provide a greater volume of EN than the more common fixed hourly rate-based feeding (RBF) method. METHODS: This single-center, randomized (3:1; VBF/RBF) prospective study evaluated critically ill patients on mechanical ventilation expected to receive EN for ≥ 3 days. Once goal rate was achieved, the randomized feeding strategy was implemented. In the VBF group, physicians used a total goal volume of feeds to determine an hourly rate. For the RBF group, physicians determined a constant hourly rate of infusion to meet goal feeds. RESULTS: Sixty-three patients were enrolled in the study with a mean age of 52.6 years (60% male). Six patients were excluded after randomization because of early extubation. The VBF group (n = 37) received 92.9% of goal caloric requirements with a mean caloric deficit of -776.0 kcal compared with the RBF group (n = 20), which received 80.9% of goal calories (P = .01) and a caloric deficit of -1933.8 kcal (P = .01). Uninterrupted EN was delivered for 51.7% of all EN days in VFB patients compared with 54.5% in RBF patients. On days when feeding was interrupted, VFB patients overall received a mean 77.6% of goal calories (while RBF patients received 61.5% of goal calories, P = .001). No vomiting, regurgitation, or feeding intolerance occurred due to VBF. CONCLUSIONS: A VBF strategy is safe and improves delivery to better meet caloric requirements than the standard more commonly used rate-based strategy.

Hepatic dysfunction in kidney transplant recipients: prevalence and impact on graft and patient survival.

BACKGROUND: Liver disease has emerged as an important cause of morbidity and mortality in renal transplant recipients. Liver insufficiency is the cause of death in up to 28% of long-term survivors after renal transplantation. The aim of this work was to evaluate the prevalence and causes of hepatic dysfunction in renal transplant recipients in Egypt, and its impact on both renal graft function and patient survival. METHODS: This study comprised 447 kidney transplant recipients who received their grafts between January 1999 and December 2003 at Mansoura Urology and Nephrology Center. Among these recipients, 104 patients showed persistent hepatic dysfunction, while the remaining 343 had normal liver function or transient hepatic dysfunction of less than 6 months' duration. RESULTS: We found that the prevalence of persistent hepatic dysfunction in our recipients was 23.3%. Infections such as hepatitis C virus (HCV;, with longer dialysis duration and blood transfusion as risk factors), HBV, and cytomegalovirus (CMV), were the main causes of persistent hepatic dysfunction. Drugs (e.g., the sirolimus and tacrolimus; cyclosporine; and azathioprine) were also associated with hepatic dysfunction. We did not find a significant impact of hepatic dysfunction on either patient or graft survival. CONCLUSIONS: Viral infections-especially HCV and CMV-were more prevalent in the group of patients with persistent hepatic dysfunction, with duration of dialysis as an important risk factor for HCV infection. Dose-dependent cyclosporine-induced hepatic dysfunction was observed early post-transplant. Neither tacrolimus- nor sirolimus-associated hepatic dysfunction was dose-dependent. Hepatic dysfunction had no significant impact on either patient or graft survival; however, this finding may be due to the relatively short duration of follow up.

Does provision of a higher Kt/V urea make a difference? A hemodialysis controversial issue.

BACKGROUND: Adequate dialysis cannot be ascertained on the sole base of a normal or even a high Kt/V(urea) so the impetus of this study was to use the neurophysiologic studies as a marker of the biologic status of the hemodialysis patients to assess the optimum level of Kt/V(urea). METHODS: This study was carried out on 20 patients (15 men and 5 women) on maintenance hemodialysis; their ages ranged from 18 to 66 years. Initially, the patients were subjected to thorough clinical and laboratory investigations, and their dialysis adequacy was assessed by studying their urea kinetic modeling and neurophysiologic studies (Phase I). Dialysis was optimized to achieve a target Kt/V(urea) of 1.3 in Phase II and 1.5 in Phase III. The duration of each phase was six months at the end of which all patients were thoroughly reevaluated. Nutrition was not manipulated during the study. RESULTS: A neurophysiologic study showed a significant improvement of polyphasicity pattern of both proximal and distal muscles of the upper and lower limbs concomitant with improvement of quality of life on achieving a Kt/V(urea) of 1.5 (p < 0.001). There was no significant change of the duration and amplitude of all studied muscles, however. CONCLUSION: Achieving a Kt/V(urea) of 1.5 is a more suitable target for hemodialysis patients because it may be an avenue for improving the neuromuscular functions of these patients.