Tetracyanonickelate (II)/KOH/reduced graphene oxide fabricated carbon felt for mediated electron transfer type electrochemical sensor for efficient detection of N2O gas at room temperature.

N2O is the most significant anthropogenic greenhouse gas, which cause the ozone depletion. Hence, the room temperature detection of N2O is highly desirable. In this work, The TCN(II)-KOH-rGO/CF modified electrode was successfully fabricated by drop coating method. The synthesized electrode was successfully characterized by SEM, TEM, FT-IR and XRD. The sensor electrode was used to detect different N2O concentration in flow conditions at room temperature. TCN(II)-KOH-rGO/CF modified electrode showed high sensitivity towards N2O, a wide range from 1ppm to 16 ppm and low detection of 1 ppm N2O were achieved for the TCN(II)-KOH-rGO/CF modified electrode. The limit of detection and the response towards this nitrogen oxide is competitive to other sensing methods. In addition, the sensitivity of the electrochemical sensor electrode was compared with the online Gas Chromatography. Additionally, the selectivity of the working electrode was analyzed and specified. The working electrode stability was analyzed for more than 30 days shows good stability. The fabricated TCN(II)-KOH-rGO/CF electrode is easier to prepare to get excellent analytical performance towards N2O. Hence, the proposed TCN(II)-KOH-rGO/CF electrode could be the suitable material for detection of N2O in the real site process.

Tumescent Local Anesthesia in Parotid Abscess - Novel Application of Old Technique.

Tumescent local anesthesia (TLA) is a regional anesthetic technique in which the diluted local anesthetic drug (commonly lidocaine) and epinephrine solution in large volume is injected subcutaneously around the site of incision. The main advantages of TLA are excellent bloodless field and longer duration of analgesia because of addition of epinephrine. Although TLA was used in various surgical procedures, there is no literature to date that has reported its use in the parotid region. Hence, we present an interesting case where this old technique found a novel application in avoiding general anesthesia and its sequelae. We also believe that it provides valuable information to doctors of various categories such as surgeons, Anesthesiologists and general practitioners/family physicians.

Skeletal toxicity resulting from exposure of growing male rats to coplanar PCB 126 is associated with disruption of calcium homeostasis and the GH-IGF-1 axis and direct effects on bone formation.

Skeletal toxicity has been reported following exposure to polychlorinated biphenyl (PCB) mixtures. However, molecular mechanisms remain poorly understood. We exposed groups of male 4-5-week-old Sprague-Dawley rats to 3,3', 4, 4', 5-pentachlorobiphenyl (PCB 126), a dioxin-like coplanar PCB congener by a single i.p. injection of 5 µmol/kg in soy oil vehicle or vehicle alone. After 4 weeks, rats were euthanized. PCB exposure resulted in hypocalcemia (P < 0.05) and significant increases in serum PTH without changes in serum phosphorous. Hyperparathyroidism was accompanied by increased expression of mRNAs of vitamin D3 metabolizing cytochrome P450 enzymes CYP27B1 and CYP24 in the kidney (P < 0.05). PCB exposure also reduced body weight, serum IGF-1, and hepatic expression of mRNAs encoding the male-specific GH-pattern-regulated CYP2C11 and CYP3A2 relative to controls (P < 0.05). PCB exposure reduced long bone length, diameter, and surface area, but increased trabecular thickness and volume (P < 0.05). Serum osteocalcin (P < 0.05), a marker and a regulator of bone formation, was reduced, but PCB exposure had no effect on the bone resorption marker RatLaps. Exposure of human intestinal Caco-2 cells to 10-100 nM PCB 126 in the presence of vitamin D3 resulted in inhibition of mRNAs for the calcium transporters TRPV6 and PMCA1b (P < 0.05). In addition, PCB 126 suppressed osteoblastogenesis in primary bone marrow mesenchymal stem cell cultures which was blunted by the AhR antagonist CH-223191. These data provide novel evidence that skeletal toxicity after exposure to PCB 126 is a result of disruption of calcium homeostasis and the GH-IGF-1 axis, and involves direct AhR-mediated effects on bone formation.

Less is more: Ebola virus surface glycoprotein expression levels regulate virus production and infectivity.

UNLABELLED: The Ebola virus (EBOV) surface glycoprotein (GP1,2) mediates host cell attachment and fusion and is the primary target for host neutralizing antibodies. Expression of GP1,2 at high levels disrupts normal cell physiology, and EBOV uses an RNA-editing mechanism to regulate expression of the GP gene. In this study, we demonstrate that high levels of GP1,2 expression impair production and release of EBOV virus-like particles (VLPs) as well as infectivity of GP1,2-pseudotyped viruses. We further show that this effect is mediated through two mechanisms. First, high levels of GP1,2 expression reduce synthesis of other proteins needed for virus assembly. Second, viruses containing high levels of GP1,2 are intrinsically less infectious, possibly due to impaired receptor binding or endosomal processing. Importantly, proteolysis can rescue the infectivity of high-GP1,2-containing viruses. Taken together, our findings indicate that GP1,2 expression levels have a profound effect on factors that contribute to virus fitness and that RNA editing may be an important mechanism employed by EBOV to regulate GP1,2 expression in order to optimize virus production and infectivity. IMPORTANCE: The Ebola virus (EBOV), as well as other members of the Filoviridae family, causes severe hemorrhagic fever that is highly lethal, with up to 90% mortality. The EBOV surface glycoprotein (GP1,2) plays important roles in virus infection and pathogenesis, and its expression is tightly regulated by an RNA-editing mechanism during virus replication. Our study demonstrates that the level of GP1,2 expression profoundly affects virus particle production and release and uncovers a new mechanism by which Ebola virus infectivity is regulated by the level of GP1,2 expression. These findings extend our understanding of EBOV infection and replication in adaptation of host environments, which will aid the development of countermeasures against EBOV infection.

Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity.

The dioxin-like PCB126 elicits toxicity in various target organs. In rat liver, an alteration in the transcript levels of several genes involved in glucose and fatty acid metabolism provides insights into the origin of its hepatotoxicity. To explore the mechanisms, male Sprague-Dawley rats, fed an AIN-93G diet, were injected with PCB126 (1 or 5 µmol/kg) or corn oil and euthanized after 2 weeks. PCB126 significantly decreased serum glucose levels and the transcript levels of genes of many gluconeogenic and glycogenolytic enzymes under the transcriptional control of a nuclear transcription factor, cAMP response element-binding protein (CREB). As a novel finding, we show that PCB126 significantly decreases CREB phosphorylation, which is important for regulating both gluconeogenesis and fatty acid oxidation in the liver and explains CREB's integrative effects on both carbohydrate and lipid metabolism in PCB126 toxicity.

Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice.

In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed "antigenic subversion." To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection.

Antigenic subversion: a novel mechanism of host immune evasion by Ebola virus.

In addition to its surface glycoprotein (GP(1,2)), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance. However such a role has not been conclusively determined for the Ebola virus sGP. In this study, we immunized mice with DNA constructs expressing GP(1,2) and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP(12) antibodies, but only from mice that have been immunized by sGP. We term this phenomenon "antigenic subversion", and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP(1,2), thereby allowing it to absorb anti-GP(1,2) antibodies. Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP(1,2) response resulting in strong cross-reactivity with sGP. This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur. Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design.

Learning cooking algorithm for solving global optimization problems.

In recent years, many researchers have made a continuous effort to develop new and efficient meta-heuristic algorithms to address complex problems. Hence, in this study, a novel human-based meta-heuristic algorithm, namely, the learning cooking algorithm (LCA), is proposed that mimics the cooking learning activity of humans in order to solve challenging problems. The LCA strategy is primarily motivated by observing how mothers and children prepare food. The fundamental idea of the LCA strategy is mathematically designed in two phases: (i) children learn from their mothers and (ii) children and mothers learn from a chef. The performance of the proposed LCA algorithm is evaluated on 51 different benchmark functions (which includes the first 23 functions of the CEC 2005 benchmark functions) and the CEC 2019 benchmark functions compared with state-of-the-art meta-heuristic algorithms. The simulation results and statistical analysis such as the t-test, Wilcoxon rank-sum test, and Friedman test reveal that LCA may effectively address optimization problems by maintaining a proper balance between exploitation and exploration. Furthermore, the LCA algorithm has been employed to solve seven real-world engineering problems, such as the tension/compression spring design, pressure vessel design problem, welded beam design problem, speed reducer design problem, gear train design problem, three-bar truss design, and cantilever beam problem. The results demonstrate the LCA's superiority and capability over other algorithms in solving complex optimization problems.

Fast random opposition-based learning Aquila optimization algorithm.

Meta-heuristic algorithms are usually employed to address a variety of challenging optimization problems. In recent years, there has been a continuous effort to develop new and efficient meta-heuristic algorithms. The Aquila Optimization (AO) algorithm is a newly established swarm-based method that mimics the hunting strategy of Aquila birds in nature. However, in complex optimization problems, the AO has shown a sluggish convergence rate and gets stuck in the local optimal region throughout the optimization process. To overcome this problem, in this study, a new mechanism named Fast Random Opposition-Based Learning (FROBL) is combined with the AO algorithm to improve the optimization process. The proposed approach is called the FROBLAO algorithm. To validate the performance of the FROBLAO algorithm, the CEC 2005, CEC 2019, and CEC 2020 test functions, along with six real-life engineering optimization problems, are tested. Moreover, statistical analyses such as the Wilcoxon rank-sum test, the t-test, and the Friedman test are performed to analyze the significant difference between the proposed algorithm FROBLAO and other algorithms. The results demonstrate that FROBLAO achieved outstanding performance and effectiveness in solving an extensive variety of optimization problems.

Paired single-B-cell transcriptomics and receptor sequencing reveal activation states and clonal signatures that characterize B cells in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML's immunological microenvironment along with their interaction with ICB remains rather constrained. METHODS: We performed an extensive analysis that involved paired single-cell RNA and B-cell receptor (BCR) sequencing on 52 bone marrow aspirate samples. These samples included 6 from healthy bone marrow donors (normal), 24 from newly diagnosed AML patients (NewlyDx), and 22 from 8 relapsed or refractory AML patients (RelRef), who underwent assessment both before and after azacitidine/nivolumab treatment. RESULTS: We delineated nine distinct subtypes of B cell lineage in the bone marrow. AML patients exhibited reduced nascent B cell subgroups but increased differentiated B cells compared with healthy controls. The limited diversity of BCR profiles and extensive somatic hypermutation indicated antigen-driven affinity maturation within the tumor microenvironment of RelRef patients. We established a strong connection between the activation or stress status of naïve and memory B cells, as indicated by AP-1 activity, and their differentiation state. Remarkably, atypical memory B cells functioned as specialized antigen-presenting cells closely interacting with AML malignant cells, correlating with AML stemness and worse clinical outcomes. In the AML microenvironment, plasma cells demonstrated advanced differentiation and heightened activity. Notably, the clinical response to ICB was associated with B cell clonal expansion and plasma cell function. CONCLUSIONS: Our findings establish a comprehensive framework for profiling the phenotypic diversity of the B cell lineage in AML patients, while also assessing the implications of immunotherapy. This will serve as a valuable guide for future inquiries into AML treatment strategies.

IMPETUS Stroke: Assessment of hospital infrastructure and workflow for implementation of uniform stroke care pathway in India.

BACKGROUND: India accounts for 13.3% of global disability-adjusted life years (DALYs) lost due to stroke with a relatively younger age of onset compared to the Western population. In India's public healthcare system, many stroke patients seek care at tertiary-level government-funded medical colleges where an optimal level of stroke care is expected. However, there are no studies from India that have assessed the quality of stroke care, including infrastructure, imaging facilities, or the availability of stroke care units in medical colleges. AIM: This study aimed to understand the existing protocols and management of acute stroke care across 22 medical colleges in India, as part of the baseline assessment of the ongoing IMPETUS stroke study. METHODS: A semi-structured quantitative pre-tested questionnaire, developed based on review of literature and expert discussion, was mailed to 22 participating sites of the IMPETUS stroke study. The questionnaire assessed comprehensively all components of stroke care, including human resources, emergency system, in-hospital care, and secondary prevention. A descriptive analysis of their status was undertaken. RESULTS: In the emergency services, limited stroke helpline numbers, 3/22 (14%); prenotification system, 5/22 (23%); and stroke-trained physicians were available, 6/22 (27%). One-third of hospitals did not have on-call neurologists. Although non-contrast computed tomography (NCCT) was always available, 39% of hospitals were not doing computed tomography (CT) angiography and 13/22 (59%) were not doing magnetic resonance imaging (MRI) after routine working hours. Intravenous thrombolysis was being done in 20/22 (91%) hospitals, but 36% of hospitals did not provide it free of cost. Endovascular therapy was available only in 6/22 (27%) hospitals. The study highlighted the scarcity of multidisciplinary stroke teams, 8/22 (36%), and stroke units, 7/22 (32%). Lifesaving surgeries like hematoma evacuation, 11/22 (50%), and decompressive craniectomy, 9/22 (41%), were performed in limited numbers. The availability of occupational therapists, speech therapists, and cognitive rehabilitation was minimal. CONCLUSION: This study highlighted the current status of acute stroke management in publicly funded tertiary care hospitals. Lack of prenotification, limited number of stroke-trained physicians and neurosurgeons, relatively lesser provision of free thrombolytic agents, limited stroke units, and lack of rehabilitation services are areas needing urgent attention by policymakers and creation of sustainable education models for uniform stroke care by medical professionals across the country.

Cytokine Release Syndrome and Associated Acute Toxicities in Pediatric Patients Undergoing Immune Effector Cell Therapy or Hematopoietic Cell Transplantation.

Immune effector cells (IEC) are a powerful and increasingly targeted tool, particularly for the control and eradication of malignant diseases. However, the infusion, expansion, and persistence of autologous or allogeneic IEC or engagement of endogenous immune cells can be associated with significant systemic multi-organ toxicities. Here we review the signs and symptoms, grading and pathophysiology of immune-related toxicities arising in the context of pediatric immunotherapies and haploidentical T cell replete Hematopoietic Cell Transplantation (HCT). Principles of management are discussed with particular focus on the intersection of these toxicities with the requirement for pediatric critical care level support.

Comparative genotoxicity of 3-hydroxyanthranilic acid and anthranilic acid in the presence of a metal cofactor Cu (II) in vitro.

Several clinical studies have reported that an increase in excretion of tryptophan metabolites 3-hydroxyanthranilic acid (3-OHAA), anthranilic acid (AA) and other metabolites in the urine of bladder cancer patients are implicated to play a role in the etiology of bladder cancer; however the mechanisms involved are unknown. The present study compares the genotoxicity of tryptophan metabolites AA and 3-OHAA to cause mutagenesis in vitro. The DNA damage effects of tryptophan metabolites were analyzed using plasmid relaxation assay performed with AA and 3-OHAA at various concentrations between 50µM and 400µM in the presence of plasmid DNA pSP-72. Both AA and 3-OHAA did not show any plasmid relaxation activity when tested alone. However, 3-OHAA in the presence of metal cofactor Cu (II) induced plasmid relaxation by causing nicks in the plasmid. This effect was not observed in the presence of other metal cofactors Fe (II) and Mn (III). Cu (II) at increasing concentrations between 5µM and 20µM and in the presence of 100µM 3-OHAA showed an apparent dose-response in causing DNA strand breaks. The Cu (II) mediated mutagenic activation of 3-OHAA was further investigated using Ames Salmonella/microsome mutagenicity assay with reactive oxygen species (ROS) sensitive tester strain Salmonella TA102. When 100µg of 3-OHAA per plate was incubated with Cu (II) a significant increase in TA102 revertants was observed with an increase in the concentration of Cu (II) from 2.5µg to 50µg. In contrast, AA with Cu (II) at such low concentration was unable to cause any significant increase in number of the TA102 revertants. This evidence for mutagenicity with only 3-OHAA and Cu (II) but not AA suggests the presence of hydroxyl group at ortho position to amino group in 3-OHAA structurally, is critical in reacting with Cu (II) to generate genotoxicity.

Barriers and Perception Towards Spectacle Wear among a Student Population of University of Buraimi, Oman.

OBJECTIVES: The study aimed to evaluate the barriers and perceptions towards spectacle wear among the student population of the University of Buraimi, Oman. METHODS: A descriptive, questionnaire-based and cross-sectional study was conducted between December 2017 and May 2018. Ophthalmic examination and a standard spectacle prescription protocol were used to identify those with inappropriate spectacle coverage. A self-designed and expert validated English-language questionnaire was utilised. A chi-square test was used to assess the association between the participants' types of perceptions and sociodemographic and refractive error-related profiles. RESULTS: In total, 275 students participated in the study (response rate: 17.19%) and 170 (61.8%) were having inappropriate spectacle correction. Only 26% of them used spectacles since the majority (73.5%) had never had their eyes examined before this study. Most perceived spectacle wear positively (53.5%), followed by some having negative (36.5%) or neutral (10.0%) perceptions. Those from a health science background including Nursing and Optometry had a higher positive perception towards spectacle wear than others (P = 0.012). The difference in the perception scores between myopic and hypermetropic refractive error groups was statistically insignificant (P = 0.882). CONCLUSION: The majority of the participants had had inappropriate vision corrections with spectacles and not undergone any prior ocular examinations. Few wore spectacles; however, these were inappropriate given their current refractive status. The reasons for spectacle non-wear were that either new spectacles had been ordered or spectacles were lost or broken. It is recommended that the school eye health initiative be extended to the university level. A holistic eye-health promotional approach toward integrating students, teachers and parents into this initiative can improve spectacle wear within the studied population.

A facile synthesis of metal ferrites and their catalytic removal of toxic nitro-organic pollutants.

Nitrocompounds are the major prime water contaminants. In this investigative study, toxic nitrocompounds (4-nitrophenol, 2,4-dinitrophenol, 2,4,6-trinitrophenol) were removed by using magnetic CuFe2O4, CoFe2O4, and NiFe2O4 material systems. The metal ferrites were synthesized through hydrothermal method and also followed with calcination process. The properties of metal ferrites were confirmed through using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and field emission scanning electron microscopy (FE-SEM) studies and results there on were presented. For the first time, the synthesized CuFe2O4, CoFe2O4, and NiFe2O4 material systems were used for the reduction of 4-nitrophenol (NP), 2,4-dinitrophenol (DNP), and 2,4,6-trinitrophenol (TNP) in aqueous medium. The UV-visible spectrometry was employed to monitor the removal of nitro compounds and formation of aminophenol. Among, the three catalysts, the CuFe2O4 displayed excellent removal activity for nitrocompounds. The CuFe2O4 nanoparticles completely removed the NP, DNP and TNP within 2, 5, 10 min, respectively. The NP reduction reaction follows the pseudo-first-order kinetics. Further, the investigated and proposed CuFe2O4, catalyst has given and demonstrated excellent kinetic rate constants 0.990, 0.317, 0.184 min-1 for 4-NP, DNP and TNP respectively, which was very fast kinetic than the already published reports. Also, the aminophenol formation was confirmed for the above mentioned and select nitrocompounds. The obtained results confirm suggest that CuFe2O4 nanoparticles based material system could be one of the promising catalysts for nitro compounds removal process.

Surface-tuned hierarchical ɤ-Fe2O3-N-rGO nanohydrogel for efficient catalytic removal and electrochemical sensing of toxic nitro compounds.

4- Nitrophenol (4-NP) is a top rated hazardous environmental pollutant and secondary explosive chemicals. For the sake of ecology and environment safety, the catalytic reduction and detection of 4-NP is highly important. In this work, ɤ-Fe2O3-nitrogen doped rGO (ɤ-Fe2O3-N-rGO) nanohydrogel was synthesized by green hydrothermal method. The morphology and phase purity of prepared ɤ-Fe2O3-N-rGO nanohydrogel were confirmed by various analytical (SEM, TEM, XRD, and XPS) and electrochemical techniques. The morphological structure of ɤ-Fe2O3-N-rGO nanohydrogel confirmed that the nanocrystals are well covered over the 2D N-rGO layer. Further, ɤ-Fe2O3-N-rGO nanohydrogel was applied for the catalytic reduction and electrochemical detection of ecotoxic 4-NP. A low cost, ɤ-Fe2O3-N-rGO nanohydrogel displayed an excellent catalytic activity, high recyclability (>5 cycles) and high conversion efficiency of 4-NP to 4-Aminophenol (4-AP). In addition, ɤ-Fe2O3-N-rGO nanohydrogel modified GCE displayed a wide linear sensing range (0.1-1000 µM), and a low detection limit (LOD) of 0.1 µM with excellent sensitivity, high selectivity (<1.2%) and good stability (>4 weeks). The developed sensor electrode shows the low reduction potential of -0.3 V and -0.60 V for the determination of 4-NP. The proposed ɤ-Fe2O3-N-rGO nanohydrogel is promising catalyst for the detection and removal of toxic aromatic nitro compounds in real site applications.

Brown-Vialetto-Van Laere syndrome: A rare case report of MND mimic.

Brown-Vialetto-Van Laere Syndrome (BVVLS) is a rare disorder characterized by progressive neuropathy, optic atrophy, hearing loss, bulbar dysfunction, and respiratory insufficiency associated with mutations in SLC52A2 and SLC52A3 genes that code for human riboflavin transporters RFVT2 and RFVT3, respectively. Nearly 70 cases have been reported by molecular diagnosis.[2],[3] The majority of familial cases are autosomal recessive[2],[4] with female to male ratio of 3:1.[5] We describe the clinical course of a 16-year-old boy with BVVLS who presented with 6 years duration of insidious onset gradually progressive sensory neural hearing loss, optic atrophy, amyotrophy of both upper limbs, and wasting of the tongue with fasciculations. Novel homozygous mutation c.1245C>T in the SLC52A2 gene was identified. At times, the clinical spectrum mimics the juvenile onset motor neuron disease (MND) as in this case. It was important to identify the BVVLS that can respond to high doses of riboflavin.

Disease Severity Assessment and Short-Term Outcome in Patients with Myasthenia Gravis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder with a chronic fluctuating course. The outcome measures encapsulate disease severity, functional impact at diagnosis, and objective evaluation of clinical benefit from therapeutic interventions. AIMS AND OBJECTIVE: To assess the disease severity, correlation between various outcome measures, and to evaluate the short-term outcome at 3 months and 6 months in a cohort of MG patients. MATERIALS AND METHODS: Quantitative myasthenia gravis (QMG) score, myasthenia gravis composite (MGC) score, and myasthenia gravis quality of life-15 (MG-QoL-15) score were applied to 54 patients at first visit, 3 months and 6 months follow-up. RESULTS: Mean quality of life-15 (QoL-15) score at base line was 15.241. Mean QMG and MGC scores at baseline were 14.63 ± 8.37 and 15.87 ± 9.14, respectively. QMG score showed a strong positive correlation with both MGC and MG-QoL-15 scores. QMG and MGC scores showed a moderate correlation with acetylcholine receptor antibody (AChR Ab) titers. Mean QMG at follow-up was 9.95 ± 5.49 at 3 months and 6.74 ± 4.74 at 6 months. Mean MGC at follow-up was 10.75 ± 5.58 at 3 months and 6.51 ± 4.36 at 6 months. CONCLUSION: The combination of physician-evaluated and patient-reported outcome measures provided a more discerning picture of patient status and response to treatment. Incorporating MG outcome measures into clinical practice would aid in modulating therapies.

The angiogenic factor midkine is regulated by dexamethasone and retinoic acid during alveolarization and in alveolar epithelial cells.

BACKGROUND: A precise balance exists between the actions of endogenous glucocorticoids (GC) and retinoids to promote normal lung development, in particular during alveolarization. The mechanisms controlling this balance are largely unknown, but recent evidence suggests that midkine (MK), a retinoic acid-regulated, pro-angiogenic growth factor, may function as a critical regulator. The purpose of this study was to examine regulation of MK by GC and RA during postnatal alveolar formation in rats. METHODS: Newborn rats were treated with dexamethasone (DEX) and/or all-trans-retinoic acid (RA) during the first two weeks of life. Lung morphology was assessed by light microscopy and radial alveolar counts. MK mRNA and protein expression in response to different treatment were determined by Northern and Western blots. In addition, MK protein expression in cultured human alveolar type 2-like cells treated with DEX and RA was also determined. RESULTS: Lung histology confirmed that DEX treatment inhibited and RA treatment stimulated alveolar formation, whereas concurrent administration of RA with DEX prevented the DEX effects. During normal development, MK expression was maximal during the period of alveolarization from postnatal day 5 (PN5) to PN15. DEX treatment of rat pups decreased, and RA treatment increased lung MK expression, whereas concurrent DEX+RA treatment prevented the DEX-induced decrease in MK expression. Using human alveolar type 2 (AT2)-like cells differentiated in culture, we confirmed that DEX and cAMP decreased, and RA increased MK expression. CONCLUSION: We conclude that MK is expressed by AT2 cells, and is differentially regulated by corticosteroid and retinoid treatment in a manner consistent with hormonal effects on alveolarization during postnatal lung development.