The influence of inhaled multi-walled carbon nanotubes on the autonomic nervous system

Background: Heart rate and cardiovascular function are regulated by the autonomic nervous system. Heart rate variability (HRV) as a marker reflects the activity of autonomic nervous system. The prognostic significance of HRV in cardiovascular disease has been reported in clinical and epidemiological studies. The present study focused on the influence of inhaled multi-walled carbon nanotubes (MWCNTs) on autonomic nervous system by HRV analysis. Methods: Male Sprague–Dawley rats were pre-implanted with a telemetry device and kept in the individual cages for recovery. At week four after device implantation, rats were exposed to MWCNTs for 5 h at a concentration of 5 mg/m3 . The real-time EKGs were recorded by a telemetry system at pre-exposure, during exposure, 1 day and 7 days post-exposure. HRV was measured by root mean square of successive differences (RMSSD); the standard deviation of inter-beat (RR) interval (SDNN); the percentage of successive RR interval differences greater than 5 ms (pNN5) and 10 ms (pNN10); low frequency (LF) and high frequency (HF). Results: Exposure to MWCNTs increased the percentage of differences between adjacent R-R intervals over 10 ms (pNN10) (p \u3c 0.01), RMSSD (p \u3c 0.01), LF (p \u3c 0.05) and HF (p \u3c 0.01). Conclusions: Inhalation of MWCNTs significantly alters the balance between sympathetic and parasympathetic nervous system. Whether such transient alterations in autonomic nervous performance would alter cardiovascular function and raise the risk of cardiovascular events in people with pre-existing cardiovascular conditions warrants further study

Antimycobacterial potential of green synthesized silver nano particles from selected Himalayan flora

Mycobacterium tuberculosis (Mtb) is a persistent threat to human life and a challenge to global public health. The pathogen’s antibioticresistance has become a serious problem, prompting the development of nanotechnology-based medicines to prevent multidrug resistance in microorganisms. The present study aimed to synthesize silver nanoparticles (AgNPs), using leaves extracts of Achillea millefolium, Artemisia campestris and Hedera nepalensis to analyze their antimycobacterial potential. The biosynthesized silver nanoparticlesnwere harvested and characterized through UV visible spectroscopy,nField Emission Scanning Electron Microscopy (FESEM) and Energy Dispersive X-ray spectroscopy (EDX). The FESEM analysis showed, that selected plant-based silver nanoparticles were spherical in shape with a diameter ranging from 50 nm to 80 nm. Energy Dispersive X-ray spectroscopy revealed that constitute elements of silver nanoparticles are Ag, C, O, Cl and Ca. The biosynthesized AgNPs exhibited significant antibacterial potential against Mycobacterium tuberculosis. At a concentration of 50 μL Hedera nepalensis exhibited the highest growth inhibition at 97.33%, followed by Artemisia at 95%, whereas the percentage growth inhibition of Achillea millefolium at 50 μL concentration was 72.33% as compared to the Rifampicin (RIF) i.e., 40%. Fluorescence microscopy confirmed visible growth inhibition in both experimental and controlled cultures. Hedra nepalensis and Artemisia campestris showed promising potential to inhibit the growth of mycobacteria populations, indicating their potential for the development of novel nanomedicine to treat tuberculosis effectively

Cardiac Autonomic Control Mechanisms in the Pathogenesis of Chagas' Heart Disease

Primary abnormalities of the autonomic nervous system had been postulated as the pathogenic mechanisms of myocardial damage, in patients with Chagas disease. However, recent investigations indicate that these abnormalities are secondary and amenable to treatment with beta-adrenergic blockers. Moreover, muscarinic cardiac autoantibodies appear to enhance parasympathetic activity on the sinus node. Therefore, the purpose of this paper is to analyze how knowledge on Chagas' disease evolved from being initially considered as a primary cardioneuromyopathy to the current status of a congestive cardiomyopathy of parasitic origin

Anticorpos muscarínicos e resposta da frequência cardíaca ao exercício dinâmico e a manobra de Valsalva na doença de Chagas crônica

We have studied the cardiac chronotropic responses to the Valsalva maneuver and to dynamic exercise of twenty chronic chagasic patients with normal left ventricular function and no segmental wall abnormalities by two-dimensional echocardiogram. The absolute increase in heart rate of the patients (Δ = 21.5 ± 10 bpm, M±SD) during the maneuver was significantly diminished when compared to controls (Δ = 31.30 ± 70, M±SD, p = 0.03). The minimum heart rate (58.24 ± 8.90 vs. 62.80 ± 10, p = 0.68) and the absolute decrease in heart rate at the end of the maneuver (Δ = 38.30 ± 13 vs. Δ = 31.47 ± 17, p = 0.10) were not different from controls. The initial heart rate acceleration during dynamic exercise (Δ = 12 ± 7.55 vs. Δ = 19 ± 7.27, M±SD, p = 0.01) was also diminished, but the heart rate recovery during the first ten seconds was more prominent in the sero-positive patients (Median: 14, Interquartile range: (9.75-17.50 vs. 5(0-8.75, p = 0.001). The serum levels of muscarinic cardiac auto-antibodies were significantly higher in the chagasic patients (Median: 34.58, Interquartile Range: 17-46.5, Optical Density) than in controls (Median: 0, Interquartile Range: 0-22.25, p = 0.001) and correlated significantly and directly (r = 0.68, p = 0.002) with early heart rate recovery during dynamic exercise. The results of this investigation indirectly suggest that, the cardiac muscarinic auto-antibodies may have positive agonist effects on parasympathetic heart rate control of chagasic patients.Foram estudadas as respostas cronotrópicas cardíacas à manobra de Valsalva e ao exercício dinâmico de vinte pacientes chagásicos com função ventricular esquerda normal e sem alterações da contractilidade segmentar por ecocardiografia bidimensional. O aumento absoluto da frequência cardíaca dos pacientes (Δ = 21,5 ± 10 bpm, M ± DP) durante a manobra de Valsalva foi significativamente menor quando se comparava ao grupo controle (Δ = 31,30 ± 70, p = 0,03). A frequência cardíaca mínima (58,24 ± 8,90 vs 62,80 ± 10, p = 0,68) e a diminuição da frequência cardíaca absoluta no final da manobra (Δ = 38,30 ± 13 vs Δ = 31,47 ± 17, p = 0,10) não foram diferentes em comparação com o grupo controle. A aceleração inicial da frequência cardíaca durante o exercício dinâmico (Δ = 12 ± 7,55 vs Δ = 19 ± 7,27, p = 0,01) também foi menor, mas a recuperação da frequência cardíaca, durante os primeiros dez segundos, foi maior no grupo sero-positivos [mediana:14 (intervalo interquartil: 9,75-17,50) vs 5 (0 - 8,75), p = 0,001]. Os níveis séricos de auto-anticorpos muscarínicos cardíacos foram significativamente maiores nos pacientes chagásicos do que no grupo controle [(mediana: 34,58 densidade óptica (intervalo interquartil 17 - 46,5) vs (mediana: 0, intervalo interquartil 0 - 22,25) p = 0,001] e a correlação é significativa e direta (r = 0,68, p = 0,002) com o início da recuperação da frequência cardíaca durante o exercício dinâmico. Os resultados desta investigação sugerem que indiretamente, os auto-anticorpos muscarínicos cardíacos, podem ter ação agonista positiva sobre o controle parassimpático da frequência cardíaca dos pacientes chagásicos

Isolation of filter passing bacteria from a range of dental clinic surfaces

Filter passing bacteria have been isolated from a variety of natural environments, appearing as a mixture of Gram-positive and Gram-negative, as well as nano-forms and wall-free species. In this study, filter passing bacteria were isolated from surfaces located in various dental departments at the College of Dentistry, King Saud University Hospital. Surface samples were obtained by using Q-tip swabs, with ten different surfaces being sampled in each clinic during pre-patient and post-patient visits. Filterable bacteria (using 0.4 and 0.2 micron filters, but not 0.1 micron filter) were isolated, being mainly Gram-positive cocci. Isolation results of filterable bacteria were compared before and after patient treatment in the clinic. More frequently, filter passing bacteria were isolated on clinic surfaces after patient treatment. The results show that dental settings are contaminated with filterable bacteria which may act as a reservoir for the wider contamination of hospital environments

Hypogammaglobulinemia: A contributing factor to multiple sclerosis fatigue?

OBJECTIVE Fatigue is one of the most disabling and difficult to treat symptoms of autoimmune diseases and frequently presents in people with multiple sclerosis (PwMS). Hypogammaglobulinemia for immunoglobulin G (IgG) affects approximately 8-25% of PwMS. We performed a retrospective analysis to investigate the association of MS-fatigue and IgG hypogammaglobulinemia. METHODS PwMS, treated at Eginition University Hospital Athens or at the University Hospital Bern, were included (n = 134 patients (Bern n = 99; Athens n = 35)). Mann Whitney U-test (MWT), ANOVA test, Chi2 test and multivariable linear regression models were run. RESULTS 97/134 (72.4%) PwMS reported fatigue. In the multivariable linear regression analysis, IgG serum concentration (-1.6, 95%CI -2.7 - -0.5, p = 0.006), daytime sleepiness (0.8, 95%CI 0.2-1.4, p = 0.009), and a depressive mood (1.1, 95%CI 0.8-1.4, p < 0.001) were significantly associated with fatigue. The impact of IgG serum concentration (-2.9 95%CI -4.7 - -1.1, p = 0.002) remained significant also in the subcohort of PwMS without depressive symptoms or daytime sleepiness. CONCLUSIONS We found an association between IgG hypogammaglobulinemia and fatigue in PwMS (Level of Evidence IV), which might be translated to other autoimmune diseases. It bears a potential therapeutic consequence considering IgG supplementation strategies, if our finding can be validated prospectively

Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer

BACKGROUND: Zoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use. CASE PRESENTATION: We report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months. CONCLUSION: Internists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology

A single nanobody neutralizes multiple epochally evolving human noroviruses by modulating capsid plasticity

Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed a conserved epitope, away from the HBGA binding site, fully accessible only when VP1 transitions to a “raised” conformation in the capsid. Together with dynamic light scattering and electron microscopy of the GII.4 VLPs, our studies suggest a mechanism in which M4 accesses the epitope by altering the conformational dynamics of the capsid and triggering its disassembly to neutralize GII.4 infection.Instituto de VirologíaFil: Salmen, Wilhelm. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Hu, Liya. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnologicas; ArgentinaFil: Bok, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chaimongkol, Natthawan. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Ettayebi, Khalil. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Sosnovtsev, Stanislav V. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Soni, Kaundal. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Ayyar, B. Vijayalakshmi. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Shanker, Sreejesh. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Neill, Frederick H. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Sankaran, Banumathi. Berkeley Center for Structural Biology. Molecular Biophysics and Integrated Bioimaging. Lawrence Berkeley Laboratory; Estados UnidosFil: Atmar, Robert L. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Atmar, Robert L. Baylor College of Medicine. Department of Medicine; Estados UnidosFil: Estes, Mary K. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados UnidosFil: Estes, Mary K. Baylor College of Medicine. Department of Medicine; Estados UnidosFil: Green, Kim Y. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Caliciviruses Section; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virologia e Innovaciones Tecnologicas (IVIT); ArgentinaFil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Prasad, B. V. Venkataram. Baylor College of Medicine. Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology; Estados UnidosFil: Prasad, B. V. Venkataram. Baylor College of Medicine. Department of Molecular Virology and Microbiology; Estados Unido

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

Clinical implications of serum neurofilament in newly diagnosed MS patients: a longitudinal multicentre cohort study

BACKGROUND: We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients. METHODS: In a multicentre prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers. Clinical parameters, MRI, and sNfL levels (measured by single molecule array) were assessed at baseline and up to four-year follow-up. FINDINGS: Of 814 patients, 54.7% (445) were diagnosed with RRMS and 45.3% (369) with CIS when applying 2010 McDonald criteria (RRMS[2010] and CIS[2010]). After reclassification of CIS[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] patients (9.1 pg/ml, IQR 6.2-13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4-20.1 pg/ml, n = 213; p = 0.036). sNfL levels correlated with number of T2 and Gd+ lesions at baseline and future clinical relapses. Patients receiving disease-modifying therapy (DMT) during the first four years had higher baseline sNfL levels than DMT-naïve patients (11.8 pg/ml, IQR 7.5-20.7 pg/ml, n = 726; 9.7 pg/ml, IQR 6.4-15.3 pg/ml, n = 88). Therapy escalation decisions within this period were reflected by longitudinal changes in sNfL levels. INTERPRETATION: Assessment of sNfL increases diagnostic accuracy, is associated with disease course prognosis and may, particularly when measured longitudinally, facilitate therapeutic decisions