Publications by authors named "Peter O"

122 Publications

Mathematical model of COVID-19 in Nigeria with optimal control.

Results Phys 2021 Sep 30;28:104598. Epub 2021 Jul 30.

Department of Mathematics, College of Science Al-Zulfi, Majmaah University, Al-Majmaah 11952, Saudi Arabia.

The novel Coronavirus Disease 2019 (COVID-19) is a highly infectious disease caused by a new strain of severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). In this work, we proposed a mathematical model of COVID-19. We carried out the qualitative analysis along with an epidemic indicator which is the basic reproduction number ( ) of this model, stability analysis of COVID-19 free equilibrium (CFE) and Endemic equilibrium (EE) using Lyaponuv function are considered. We extended the basic model into optimal control system by incorporating three control strategies. These are; use of face-mask and hand sanitizer along with social distancing; treatment of COVID-19 patients and active screening with testing and the third control is prevention against recurrence and reinfection of humans who have recovered from COVID-19. Daily data given by Nigeria Center for Disease Control (NCDC) in Nigeria is used for simulation of the proposed COVID-19 model to see the effects of the control measures. The biological interpretation of this findings is that, COVID-19 can be effectively managed or eliminated in Nigeria if the control measures implemented are capable of taking or sustaining the basic reproductive number to a value below unity. If the three control strategies are well managed by the government namely; NCDC, Presidential Task Force (PTF) and Federal Ministry of Health (FMOH) or policymakers, then COVID-19 in Nigeria will be eradicated.
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http://dx.doi.org/10.1016/j.rinp.2021.104598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323584PMC
September 2021

A new mathematical model of COVID-19 using real data from Pakistan.

Results Phys 2021 May 31;24:104098. Epub 2021 Mar 31.

Department of Mathematics, University of Ilorin, Ilorin, Nigeria.

We propose a new mathematical model to investigate the recent outbreak of the coronavirus disease (COVID-19). The model is studied qualitatively using stability theory of differential equations and the basic reproductive number that represents an epidemic indicator is obtained from the largest eigenvalue of the next-generation matrix. The global asymptotic stability conditions for the disease free equilibrium are obtained. The real COVID-19 incidence data entries from 01 July, 2020 to 14 August, 2020 in the country of Pakistan are used for parameter estimation thereby getting fitted values for the biological parameters. Sensitivity analysis is performed in order to determine the most sensitive parameters in the proposed model. To view more features of the state variables in the proposed model, we perform numerical simulations by using different values of some essential parameters. Moreover, profiles of the reproduction number through contour plots have been biologically explained.
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http://dx.doi.org/10.1016/j.rinp.2021.104098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010333PMC
May 2021

COVID-19 and the ethical issues of justice and rationing in health care, with particular regard to the Italian experience

Orv Hetil 2020 11 8;161(45):1899-1907. Epub 2020 Nov 8.

1Általános Orvostudományi Kar, Magatartástudományi Intézet, Semmelweis Egyetem, Budapest, Nagyvárad tér 4., 1089.

Összefoglaló. A 2020. év elején kirobbant COVID-19-világjárvány többek között ráirányította a figyelmet az életmentő-életfenntartó kezelések igazságos elosztásának érzékeny kérdésére is. Európán belül elsőként Olaszországot sújtotta a katasztrófa, a válsághelyzetben pedig az érzéstelenítés, fájdalomcsillapítás, újraélesztés és intenzív ellátás területén tevékenykedő szakemberek olasz társasága, a SIAARTI 2020. március 6-án közzétett egy 15 pontos ajánlást. E szerint utilitarista megközelítéssel a rendelkezésre álló szűkös erőforrásokat azon betegek kezelésére kellene fordítani, akik túlélési esélye nagyobb, valamint több életévre számíthatnak a jövőben, mert ez biztosíthatja a lehető legtöbb ember számára a lehető legnagyobb hasznot. A javaslat komoly szakmai vitát robbantott ki, amely egyértelművé tette, hogy az orvosi eszközök igazságos elosztására vonatkozó diskurzust feltétlenül folytatni kell, nemcsak Olaszországon belül, hanem a pandémiától sújtott többi államban is. Orv Hetil. 2020; 161(45): 1899-1907. Summary. Among other queries, the explosion of the COVID-19 pandemic at the beginning of 2020 has firmly put in focus the sensitive issue of how to allocate scarcely available life-saving treatments in a fair and just manner. The first European country to face an emergency caused by the pandemic was Italy. In a rapidly escalating crisis, on 6th March 2020, the Italian Society of Anaesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI) issued a series of 15 recommendations, suggesting that a utilitarian approach should be adopted in Italian health care and the extremely scarce resources should be reserved for patients with a greater probability of survival and life expectancy, in order to maximize the benefits for the largest possible number of people. The recommendations generated a heated debate among health care professionals, thereby evidencing that similar discussions must be initiated and pursued in all countries affected by the pandemic. Orv Hetil. 2020; 161(45): 1899-1907.
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http://dx.doi.org/10.1556/650.2020.32043DOI Listing
November 2020

Fatal consequences of uterine rupture in late pregnancy.

Soud Lek 2020 ;65(3):65-66

Uterine rupture in pregnancy belongs to acute conditions in gynaecology and obstetrics. It is a life-threatening complication for both mother and foetus. The occurrence of fatal consequences in developed countries is very rare. The causes of rupture include scarring after the caesarean section, fibroid enucleation, rough curettage, muscular insufficiency in uterine developmental defects, uterine wall damage due to inflammation, uterine hypoplasia, elevated intrauterine pressure during contraction, cephalopelvic disproportion, previous fibroid, prostaglandin or oxytocin administration, etc. This paper aims at the presentation of a 32-year-old woman who died in the 35th week of gestation due to uterine rupture at home despite having been transferred to a medical facility at the terminal stage of life. At the autopsy, a complete rupture of the posterior uterine wall with bleeding into the abdominal cavity and an amniotic sac with a male foetus in the abdominal cavity was found. There were no signs of the effects of violence detected. Histopathological examination revealed no pathological changes in the uterine muscle. The immediate cause of maternal death was a haemorrhagic shock. The autopsy of the foetus revealed signs of asphyxia. The immediate cause of foetal death was intrauterine asphyxia. In this case, forensic expertise ruled out the violent causes of uterine rupture and deaths in terms of mechanical and chemical factors and supported to make a diagnosis of spontaneous rupture.
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December 2020

Appendiceal fibroma in an Amyand's hernia mimicking a supernumerary testis: a case report.

Trop Doct 2020 Oct 9;50(4):380-383. Epub 2020 Jul 9.

Associate Professor/Consultant Urologist, Department of Surgery, 58989Ahmadu Bello University, Zaria, Nigeria.

Amyand's hernia describes the presence of an appendix within the sac of an inguinal hernia. Both an inflamed and non-inflamed appendix within the hernia sac have been reported in the literature with various recommendations on approach to management. However, a tumour of the appendix is a rare finding in an Amyand's hernia. We hereby report the unusual presentation of a fibroma of the appendix complicating the rare Amyand's hernia in a young man with a scrotal mass.
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http://dx.doi.org/10.1177/0049475520937109DOI Listing
October 2020

Appendiceal fibroma in an Amyand's hernia mimicking a supernumerary testis: a case report.

Trop Doct 2020 Oct 9;50(4):380-383. Epub 2020 Jul 9.

Associate Professor/Consultant Urologist, Department of Surgery, 58989Ahmadu Bello University, Zaria, Nigeria.

Amyand's hernia describes the presence of an appendix within the sac of an inguinal hernia. Both an inflamed and non-inflamed appendix within the hernia sac have been reported in the literature with various recommendations on approach to management. However, a tumour of the appendix is a rare finding in an Amyand's hernia. We hereby report the unusual presentation of a fibroma of the appendix complicating the rare Amyand's hernia in a young man with a scrotal mass.
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http://dx.doi.org/10.1177/0049475520937109DOI Listing
October 2020

Appendiceal fibroma in an Amyand's hernia mimicking a supernumerary testis: a case report.

Trop Doct 2020 Oct 9;50(4):380-383. Epub 2020 Jul 9.

Associate Professor/Consultant Urologist, Department of Surgery, 58989Ahmadu Bello University, Zaria, Nigeria.

Amyand's hernia describes the presence of an appendix within the sac of an inguinal hernia. Both an inflamed and non-inflamed appendix within the hernia sac have been reported in the literature with various recommendations on approach to management. However, a tumour of the appendix is a rare finding in an Amyand's hernia. We hereby report the unusual presentation of a fibroma of the appendix complicating the rare Amyand's hernia in a young man with a scrotal mass.
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http://dx.doi.org/10.1177/0049475520937109DOI Listing
October 2020

Novel high-throughput myofibroblast assays identify agonists with therapeutic potential in pulmonary fibrosis that act via EP2 and EP4 receptors.

PLoS One 2018 28;13(11):e0207872. Epub 2018 Nov 28.

Idorsia Pharmaceuticals Ltd., Allschwil, Switzerland.

Pathological features of pulmonary fibrosis include accumulation of myofibroblasts and increased extracellular matrix (ECM) deposition in lung tissue. Contractile α-smooth muscle actin (α-SMA)-expressing myofibroblasts that produce and secrete ECM are key effector cells of the disease and therefore represent a viable target for potential novel anti-fibrotic treatments. We used primary normal human lung fibroblasts (NHLF) in two novel high-throughput screening assays to discover molecules that inhibit or revert fibroblast-to-myofibroblast differentiation. A phenotypic high-content assay (HCA) quantified the degree of myofibroblast differentiation, whereas an impedance-based assay, multiplexed with MS / MS quantification of α-SMA and collagen 1 alpha 1 (COL1) protein, provided a measure of contractility and ECM formation. The synthetic prostaglandin E1 (PGE1) alprostadil, which very effectively and potently attenuated and even reversed TGF-β1-induced myofibroblast differentiation, was identified by screening a library of approved drugs. In TGF-β1-induced myofibroblasts the effect of alprostadil was attributed to activation of prostanoid receptor 2 and 4 (EP2 and EP4, respectively). However, selective activation of the EP2 or the EP4 receptor was already sufficient to prevent or reverse TGF-β1-induced NHLF myofibroblast transition. Our high-throughput assays identified chemical structures with potent anti-fibrotic properties acting through potentially novel mechanisms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207872PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261607PMC
April 2019

Prevalence of tick-borne pathogens in questing Ixodes ricinus ticks in urban and suburban areas of Switzerland.

Parasit Vectors 2017 Nov 9;10(1):558. Epub 2017 Nov 9.

Spiez Laboratory, Federal Office for Civil Protection, Austrasse, Spiez, Switzerland.

Background: Throughout Europe, Ixodes ricinus transmits numerous pathogens. Its widespread distribution is not limited to rural but also includes urbanized areas. To date, comprehensive data on pathogen carrier rates of I. ricinus ticks in urban areas of Switzerland is lacking.

Results: Ixodes ricinus ticks sampled at 18 (sub-) urban collection sites throughout Switzerland showed carrier rates of 0% for tick-borne encephalitis virus, 18.0% for Borrelia burgdorferi (sensu lato), 2.5% for Borrelia miyamotoi, 13.5% for Rickettsia spp., 1.4% for Anaplasma phagocytophilum, 6.2% for "Candidatus Neoehrlichia mikurensis", and 0.8% for Babesia venatorum (Babesia sp., EU1). Site-specific prevalence at collection sites with n > 45 ticks (n = 9) significantly differed for B. burgdorferi (s.l.), Rickettsia spp., and "Ca. N. mikurensis", but were not related to the habitat type. Three hundred fifty eight out of 1078 I. ricinus ticks (33.2%) tested positive for at least one pathogen. Thereof, about 20% (71/358) were carrying two or three different potentially disease-causing agents. Using next generation sequencing, we could detect true pathogens, tick symbionts and organisms of environmental or human origin in ten selected samples.

Conclusions: Our data document the presence of pathogens in the (sub-) urban I. ricinus tick population in Switzerland, with carrier rates as high as those in rural regions. Carriage of multiple pathogens was repeatedly observed, demonstrating the risk of acquiring multiple infections as a consequence of a tick bite.
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http://dx.doi.org/10.1186/s13071-017-2500-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680829PMC
November 2017

The Screening Compound Collection: A Key Asset for Drug Discovery.

Chimia (Aarau) 2017 Oct;71(10):667-677

Drug Discovery & Preclinical Development Idorsia Pharmaceuticals Ltd Hegenheimermattweg 91, CH-4123 Allschwil.

In this case study on an essential instrument of modern drug discovery, we summarize our successful efforts in the last four years toward enhancing the Actelion screening compound collection. A key organizational step was the establishment of the Compound Library Committee (CLC) in September 2013. This cross-functional team consisting of computational scientists, medicinal chemists and a biologist was endowed with a significant annual budget for regular new compound purchases. Based on an initial library analysis performed in 2013, the CLC developed a New Library Strategy. The established continuous library turn-over mode, and the screening library size of 300'000 compounds were maintained, while the structural library quality was increased. This was achieved by shifting the selection criteria from 'druglike' to 'leadlike' structures, enriching for non-flat structures, aiming for compound novelty, and increasing the ratio of higher cost 'Premium Compounds'. Novel chemical space was gained by adding natural compounds, macrocycles, designed and focused libraries to the collection, and through mutual exchanges of proprietary compounds with agrochemical companies. A comparative analysis in 2016 provided evidence for the positive impact of these measures. Screening the improved library has provided several highly promising hits, including a macrocyclic compound, that are currently followed up in different Hit-to-Lead and Lead Optimization programs. It is important to state that the goal of the CLC was not to achieve higher HTS hit rates, but to increase the chances of identified hits to serve as the basis of successful early drug discovery programs. The experience gathered so far legitimates the New Library Strategy.
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http://dx.doi.org/10.2533/chimia.2017.667DOI Listing
October 2017

Goats as sentinel hosts for the detection of tick-borne encephalitis risk areas in the Canton of Valais, Switzerland.

BMC Vet Res 2017 Jul 11;13(1):217. Epub 2017 Jul 11.

Institute of Biology, Laboratory of Ecology and Evolution of parasites, University of Neuchâtel, Rue Emile-Argand 11, 2000, Neuchâtel, Neuchâtel, Switzerland.

Background: Tick-borne encephalitis (TBE) is an important tick-borne disease in Europe. Detection of the TBE virus (TBEV) in local populations of Ixodes ricinus ticks is the most reliable proof that a given area is at risk for TBE, but this approach is time-consuming and expensive. A cheaper and simpler approach is to use immunology-based methods to screen vertebrate hosts for TBEV-specific antibodies and subsequently test the tick populations at locations with seropositive animals.

Results: The purpose of the present study was to use goats as sentinel animals to identify new risk areas for TBE in the canton of Valais in Switzerland. A total of 4114 individual goat sera were screened for TBEV-specific antibodies using immunological methods. According to our ELISA assay, 175 goat sera reacted strongly with TBEV antigen, resulting in a seroprevalence rate of 4.3%. The serum neutralization test confirmed that 70 of the 173 ELISA-positive sera had neutralizing antibodies against TBEV. Most of the 26 seropositive goat flocks were detected in the known risk areas in the canton of Valais, with some spread into the connecting valley of Saas and to the east of the town of Brig. One seropositive site was 60 km to the west of the known TBEV-endemic area. At two of the three locations where goats were seropositive, the local tick populations also tested positive for TBEV.

Conclusion: The combined approach of screening vertebrate hosts for TBEV-specific antibodies followed by testing the local tick population for TBEV allowed us to detect two new TBEV foci in the canton of Valais. The present study showed that goats are useful sentinel animals for the detection of new TBEV risk areas.
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http://dx.doi.org/10.1186/s12917-017-1136-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504567PMC
July 2017

Evaluation of a companion robot based on field tests with single older adults in their homes.

Assist Technol 2018 19;30(5):259-266. Epub 2017 Jun 19.

a Medical-Engineering Rehabilitation Research Programme, National Institute for Medical Rehabilitation , Budapest , Hungary.

The growing number of older adults places insurmountable load on family members and professional caregivers. Assistive technology with the aid of robots can present a possible solution. The goal of this article was to test a companion robot supporting older adults in their home environments. Eight senior volunteers were involved in the field test. They all lived alone and were self-supporting. The robot was capable of providing cognitive assistance to manage the user's daily routine. Each participant used the robot for 94.9 ± 19.6 days. The primary communication modality was voice communication in their natural language, while the touch screen display was also available for interaction with the robot. The assistance given in daily living was evaluated by subjective (the user's opinion) and objective (logged data) criteria. The most useful and the least reliable robot functions according to the users were the navigation and the verbal communication. Entertainment, locomotion, and weather forecast were the most frequently used functions, while the shopping list was the least popular. The companion robot used in the test was accepted enthusiastically by the senior subjects. Specific robot functions (mainly navigation in the apartment and the speech recognition) require improvement to better accommodate real circumstances.
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http://dx.doi.org/10.1080/10400435.2017.1322158DOI Listing
October 2019

Effect of Green Tea Polyphenol Epigallocatechin-3-gallate on the Aggregation of αA(66-80) Peptide, a Major Fragment of αA-crystallin Involved in Cataract Development.

Curr Eye Res 2017 10 19;42(10):1368-1377. Epub 2017 Jun 19.

a Department of Biotechnology , Central University of Rajasthan , NH-8 Bandarsindri, Kishangarh Ajmer , Rajasthan , India.

Purpose: Crystallin is a major protein present in eye lens. Peptide fragment αA(66-80) derived from αA-crystallin possesses high aggregation propensity and forms amyloid-like structures. αA(66-80) aggregates are known to interact with soluble crystallins and destabilize native structures that subsequently undergo aggregation. Crystallin aggregation in eye lens leads to reduction in lens opacity, the condition generally referred to as a cataract. Thus, αA(66-80) aggregation appears to be an important event during cataract development, and therefore, inhibition of αA(66-80) aggregation may be an attractive strategy to intervene in cataract development.

Materials And Methods: αA(66-80) peptide derived from αA-crystallin possesses high aggregation potential and has a crucial role in cataract development. In order to inhibit the aggregation of αA(66-80) peptide, epigallocatechin-3-gallate (EGCG), a major active constituent of green tea, was employed. The inhibitory effect was assessed by Congo Red (CR) spectral shift assay, Thioflavin-T binding assay, transmission electron microscopy and fluorescence microscopy.

Results: The inhibitory potential of EGCG toward αA-crystallin was clearly observed as in the presence of EGCG, the αA(66-80) aggregation was considerably inhibited and the pre-formed fibrillary aggregates of αA(66-80) were found to be disassembled.

Conclusion: In the present study, we are able to successfully demonstrate that EGCG efficiently blocks the aggregation of αA(66-80) peptide in a concentration-dependent manner. Furthermore, it is also evident that EGCG is able to disaggregate pre-formed αA(66-80) aggregates. The study suggests that EGCG can be a potential molecule that can prevent the initiation of cataract as well as be helpful in the disease reversal.
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http://dx.doi.org/10.1080/02713683.2017.1324628DOI Listing
October 2017

Exercising daily living activities in robot-mediated therapy.

J Phys Ther Sci 2017 May 16;29(5):854-858. Epub 2017 May 16.

National Institute for Medical Rehabilitation, Hungary.

[Purpose] Investigation of the efficacy of robot-mediated therapy of the upper limb in patients with chronic stroke, in task-oriented training activities of daily living in real environment. [Subjects and Methods] 20 patients, each more than one year post-stroke (13-71 months) received 20 sessions of upper limb robot-mediated therapy. No other treatment was given. Each therapy session consisted of a passive motion and an active task therapy. During the active therapy, subjects exercised 5 activities of daily living. Assessments of the subjects were blind, and conducted one month prior to, at the start, at the end, and three months after the therapy course. The following outcome measures were recorded: Fugl-Meyer Scale-upper extremity subsection, Modified Ashworth Scale, Action Research Arm Test, Functional Independence Measure, Barthel Index. [Results] Significant improvements were observed between the start and the end of the therapy, except for Modified Ashworth Scale and Barthel Index. Results still held up at the follow-up visit three months later. [Conclusion] Practicing activities of daily living in real environment with robot-mediated physical therapy can improve the motor and functional ability of patients, even with relatively good initial functions, and even years post-stroke.
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http://dx.doi.org/10.1589/jpts.29.854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462686PMC
May 2017

["The Diagnosis is not me - But it is a Part of me" - An In-Depth Interview Study on Perspectives of Mentally Ill People].

Psychiatr Prax 2019 01 3;46(1):27-33. Epub 2017 Apr 3.

Kath. Hochschule Nordrhein-Westfalen/Aachen, Institut für Gesundheitsforschung und Soziale Psychiatrie (igsp), Aachen.

Objective: This study aimed at investigating how mentally ill people experience and evaluate their diagnosis.

Methods: 16 in-depth interviews with patients with different mental health diagnosis were carried out. The interviews were transcribed and analyzed using content analysis methods.

Results: The study participants reported rejection and stigma experiences in many areas of their life. On the other hand, they consider the diagnosis as necessary guidance and important starting-point for changes. Dealing with the diagnosis is often described as a long-term process which changes the perception of the illness and the person's own self-concept lastingly.

Conclusions: The "adoption" of a mental health diagnosis is a protracted, complex and often painful identity-related process for the people affected. This process should be supported by suitable counselling services.
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http://dx.doi.org/10.1055/s-0043-100026DOI Listing
January 2019

Naringin Ameliorates HIV-1 Nucleoside Reverse Transcriptase Inhibitors- Induced Mitochondrial Toxicity.

Curr HIV Res 2016 ;14(6):506-516

Department of Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville campus, Durban 4001, South Africa.

Background: Mitochondrial reactive oxygen species (ROS) generation and defective oxidative phosphorylation (OXPHOS) have been proposed as possible mechanisms underlying the development of nucleoside reverse transcriptase inhibitors (NRTIs)-induced mitochondrial toxicities. Available options in managing these complications have, so far, produced controversial results, thus necessitating further research into newer agents with promise. Antioxidant and free-radical scavenging effects of naringin, a plant-derived flavonoid, have previously been demonstrated.

Objective: This study was designed to investigate the effects of naringin on NRTIs-induced mitochondrial toxicity.

Methods: Wistar rats were randomly divided into Zidovudine (AZT)-only (100 mg/kg body weight BW); AZT+Naringin (100+50 mg/kg BW); AZT+Vitamin E (100+100 mg/kg BW); Stavudine (d4T)- only (50 mg/kg BW); d4T+Naringin (50+50 mg/kg BW); d4T+Vitamin E (50+100 mg/kg BW) and Vehicle (3.0 mL/kg BW)-treated groups, respectively. After 56 days of oral daily dosing, rats were euthanized by halothane overdose, blood collected by cardiac puncture and livers promptly excised for further biochemical and ultrastructural analyses. </p> Results: AZT- or d4T-only caused significant mitochondrial dysfunction and mitochondrial ultrastructural damage compared to controls, while either naringin or vitamin E reversed indices of mitochondrial dysfunction evidenced by significantly reduced mitochondrial malondialdehyde (MDA) and blood lactate concentrations, increased liver manganese superoxide dismutase (MnSOD) activity and upregulate expression of mitochondrial-encoded subunit of electron transport chain (ETC) complex IV protein compared to AZT- or d4T-only treated rats. Furthermore, naringin or vitamin E, respectively, ameliorated mitochondrial damage observed in AZT- or d4T-only treated rats.

Conclusion: Naringin ameliorated oxidative stress and NRTI-induced mitochondrial damage and might, therefore, be beneficial in managing toxicities and complications arising from NRTI use.
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http://dx.doi.org/10.2174/1570162x14666160520114639DOI Listing
August 2017

Evaluation of a new serological test for the detection of anti-Coxiella and anti-Rickettsia antibodies.

Microbes Infect 2015 Nov-Dec;17(11-12):811-6. Epub 2015 Sep 30.

Institute of Microbiology, University of Lausanne, University Hospital Center, Lausanne, Switzerland. Electronic address:

Coxiella burnetii and members of the genus Rickettsia are obligate intracellular bacteria. Since cultivation of these organisms requires dedicated techniques, their diagnosis usually relies on serological or molecular biology methods. Immunofluorescence is considered the gold standard to detect antibody-reactivity towards these organisms. Here, we assessed the performance of a new automated epifluorescence immunoassay (InoDiag) to detect IgM and IgG against C. burnetii, Rickettsia typhi and Rickettsia conorii. Samples were tested with the InoDiag assay. A total of 213 sera were tested, of which 63 samples from Q fever, 20 from spotted fever rickettsiosis, 6 from murine typhus and 124 controls. InoDiag results were compared to micro-immunofluorescence. For acute Q fever, the sensitivity of phase 2 IgG was only of 30% with a cutoff of 1 arbitrary unit (AU). In patients with acute Q fever with positive IF IgM, sensitivity reached 83% with the same cutoff. Sensitivity for chronic Q fever was 100% whereas sensitivity for past Q fever was 65%. Sensitivity for spotted Mediterranean fever and murine typhus were 91% and 100%, respectively. Both assays exhibited a good specificity in control groups, ranging from 79% in sera from patients with unrelated diseases or EBV positivity to 100% in sera from healthy patients. In conclusion, the InoDiag assay exhibits an excellent performance for the diagnosis of chronic Q fever but a very low IgG sensitivity for acute Q fever likely due to low reactivity of phase 2 antigens present on the glass slide. This defect is partially compensated by the detection of IgM. Because it exhibits a good negative predictive value, the InoDiag assay is valuable to rule out a chronic Q fever. For the diagnosis of rickettsial diseases, the sensitivity of the InoDiag method is similar to conventional immunofluorescence.
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http://dx.doi.org/10.1016/j.micinf.2015.09.015DOI Listing
October 2016

Exposure to low doses of Coxiella burnetii caused high illness attack rates: Insights from combining human challenge and outbreak data.

Epidemics 2015 Jun 31;11:1-6. Epub 2014 Dec 31.

Centre for Infectious Disease Control, RIVM, Bilthoven, The Netherlands; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

Background: As a major zoonotic pathogen, characterization of the infectivity and pathogenicity of Coxiella burnetii is essential to understand Q-fever epidemiology.

Objectives: We want to extend a recently published human dose response model based on experimental challenge of young adult males to include other age groups and both genders. Additionally, we can estimate the spatial distribution of exposure based on observed outbreak data.

Methods: Dose response assessment based on human challenge, is extended by including outbreak data, using location of cases as a proxy for exposure. This allows estimation of the influence of age and gender on the probability of developing symptoms of acute respiratory illness.

Results: In an outbreak in Switzerland, in 1983, exposure to C. burnetii was shown to depend strongly on distance from the source. The susceptibility of males to develop Q-fever decreases with age, while in females, middle-aged women appear to have the lowest risk.

Conclusions: The published dose response model for Q-fever, based on experimental challenge of a small group of human volunteers, has been updated with data from a well studied outbreak. Infectivity estimates remain high, and even low doses (of 10 or fewer organisms) cause a high risk of illness.
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http://dx.doi.org/10.1016/j.epidem.2014.12.004DOI Listing
June 2015

Q fever outbreak in the terraced vineyards of Lavaux, Switzerland.

New Microbes New Infect 2014 Jul 16;2(4):93-9. Epub 2014 Jul 16.

Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland ; Institute of Microbiology, Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne, Switzerland.

Coxiella burnetii infection (Q fever) is a widespread zoonosis with low endemicity in Switzerland, therefore no mandatory public report was required. A cluster of initially ten human cases of acute Q fever infections characterized by prolonged fever, asthenia and mild hepatitis occurred in 2012 in the terraced vineyard of Lavaux. Epidemiological investigations based on patients' interviews and veterinary investigations included environmental sampling as well as Coxiella-specific serological assay and molecular examinations (real-time PCR in vaginal secretions) of suspected sheep. These investigations demonstrated that 43% of sheep carried the bacteria whereas 30% exhibited anti-Coxiella antibodies. Mitigation measures, including limiting human contacts with the flock, hygiene measures, flock vaccination and a public official alert, have permitted the detection of four additional human cases and the avoidance of a much larger outbreak. Since November 2012, mandatory reporting of Q fever to Swiss public health authorities has been reintroduced. A close follow up of human cases will be necessary to identify chronic Q fever.
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http://dx.doi.org/10.1002/nmi2.37DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184577PMC
July 2014

Development of a high throughput PCR to detect Coxiella burnetii and its application in a diagnostic laboratory over a 7-year period.

New Microbes New Infect 2013 Oct 18;1(1):6-12. Epub 2013 Sep 18.

Institute of Microbiology, University Hospital of Lausanne Lausanne, Switzerland.

Q fever is a worldwide zoonotic infectious disease due to Coxiella burnetii. The clinical presentation may be acute (pneumonia and/or hepatitis) or chronic (most commonly endocarditis). Diagnosis mainly relies on serology and PCR. We therefore developed a quantitative real-time PCR. We first tested blindly its performance on various clinical samples and then, when thoroughly validated, we applied it during a 7-year period for the diagnosis of both acute and persistent C. burnetii infection. Analytical sensitivity (< 10 copies/PCR) was excellent. When tested blindly on 183 samples, the specificity of the PCR was 100% (142/142) and the sensitivity was 71% (29/41). The sensitivity was 88% (7/8) on valvular samples, 69% (20/29) on blood samples and 50% (2/4) on urine samples. This new quantitative PCR was then successfully applied for the diagnosis of acute Q fever and endovascular infection due to C. burnetii, allowing the diagnosis of Q fever in six patients over a 7-year period. During a local small cluster of cases, the PCR was also applied to blood from 1355 blood donors; all were negative confirming the high specificity of this test. In conclusion, we developed a highly specific method with excellent sensitivity, which may be used on sera for the diagnosis of acute Q fever and on various samples such as sera, valvular samples, aortic specimens, bone and liver, for the diagnosis of persistent C. burnetii infection.
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http://dx.doi.org/10.1002/2052-2975.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184484PMC
October 2013

Prevalence and phylogenetic analysis of tick-borne encephalitis virus (TBEV) in field-collected ticks (Ixodes ricinus) in southern Switzerland.

Parasit Vectors 2014 Sep 22;7:443. Epub 2014 Sep 22.

Central Institute of Valais Hospitals, Infectious diseases, Av Grand Champsec 86, Sion, Switzerland.

Background: Tick-borne encephalitis is the most common tick-borne viral infection in Europe with 3,000 human cases reported each year. In Western Europe, the castor bean tick, Ixodes ricinus, is the principal vector of the tick-borne encephalitis virus (TBEV). TBEV appears to be spreading geographically and was recently detected for the first time in Canton Valais in the southern part of Switzerland. The purpose of the present study was to survey the I. ricinus tick populations of Canton Valais for TBEV.

Methods: We collected a total of 19,331 I. ricinus ticks at 45 different sites in Canton Valais between 2010 and 2013. Ticks were processed in pools and tested for TBEV using reverse transcription quantitative PCR. The NS5 gene and the envelope gene of the TBEV isolates were partially sequenced for phylogenetic analysis.

Results: TBEV was detected in tick populations at six of the 45 sites. These six sites were all located in a 33 km transect along the Rhône River. TBEV was detected in two sites for three of the four years of the study showing the temporal persistence of the pathogen. Prevalence of TBEV in the six positive sites ranged from 0.16% to 11.11%. Phylogenetic analysis found that all TBEV isolates from Canton Valais belonged to the European subtype. Genetic analysis found two distinct lineages of TBEV suggesting that Canton Valais experienced two independent colonization events.

Conclusions: TBEV appears to be well established at certain locations in Canton Valais.
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http://dx.doi.org/10.1186/1756-3305-7-443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261884PMC
September 2014

A real-time research platform to study vestibular implants with gyroscopic inputs in vestibular deficient subjects.

IEEE Trans Biomed Circuits Syst 2014 Aug;8(4):474-84

Researchers have succeeded in partly restoring damaged vestibular functionality in several animal models. Recently, acute interventions have also been demonstrated in human patients. Our previous work on a vestibular implant for humans used predefined stimulation patterns; here we present a research tool that facilitates motion-modulated stimulation. This requires a system that can process gyroscope measurements and send stimulation parameters to a hybrid vestibular-cochlear implant in real-time. To match natural vestibular latencies, the time from sensor input to stimulation output should not exceed 6.5 ms. We describe a system based on National Instrument's CompactRIO platform that can meet this requirement and also offers floating point precision for advanced transfer functions. It is designed for acute clinical interventions, and is sufficiently powerful and flexible to serve as a development platform for evaluating prosthetic control strategies. Amplitude and pulse frequency modulation to predetermined functions or sensor inputs have been validated. The system has been connected to human patients, who each have received a modified MED-EL cochlear implant for vestibular stimulation, and patient tests are ongoing.
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http://dx.doi.org/10.1109/TBCAS.2013.2290089DOI Listing
August 2014

Presence of Chlamydiales DNA in ticks and fleas suggests that ticks are carriers of Chlamydiae.

Ticks Tick Borne Dis 2014 Jun 31;5(4):359-65. Epub 2014 Mar 31.

Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland. Electronic address:

The Chlamydiales order includes the Chlamydiaceae, Parachlamydiaceae, Waddliaceae, Simkaniaceae, Criblamydiaceae, Rhabdochlamydiaceae, Clavichlamydiaceae, and Piscichlamydiaceae families. Members of the Chlamydiales order are obligate intracellular bacteria that replicate within eukaryotic cells of different origins including humans, animals, and amoebae. Many of these bacteria are pathogens or emerging pathogens of both humans and animals, but their true diversity is largely underestimated, and their ecology remains to be investigated. Considering their potential threat on human health, it is important to expand our knowledge on the diversity of Chlamydiae, but also to define the host range colonized by these bacteria. Thus, using a new pan-Chlamydiales PCR, we analyzed the prevalence of Chlamydiales DNA in ticks and fleas, which are important vectors of several viral and bacterial infectious diseases. To conduct this study, 1340 Ixodes ricinus ticks prepared in 192 pools were collected in Switzerland and 55 other ticks belonging to different tick species and 97 fleas belonging to different flea species were harvested in Algeria. In Switzerland, the prevalence of Chlamydiales DNA in the 192 pools was equal to 28.1% (54/192) which represents an estimated prevalence in the 1340 individual ticks of between 4.0% and 28.4%. The pan-Chlamydiales qPCR was positive for 45% (25/55) of tick samples collected in Algeria. The sequencing of the positive qPCR amplicons revealed a high diversity of Chlamydiales species. Most of them belonged to the Rhabdochlamydiaceae and Parachlamydiaceae families. Thus, ticks may carry Chlamydiales and should thus be considered as possible vectors for Chlamydiales propagation to both humans and animals.
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http://dx.doi.org/10.1016/j.ttbdis.2013.11.009DOI Listing
June 2014

Home care robot for socially supporting the elderly: focus group studies in three European countries to screen user attitudes and requirements.

Int J Rehabil Res 2013 Dec;36(4):375-8

aNational Institute for Medical Rehabilitation bSzent János Hospital cBudapest University of Technology and Economics, Budapest, Hungary dInstitute of Design and Assessment of Technology, Vienna University of Technology, Vienna, Austria eCentral Hospital of University of Toulouse, Toulouse, France.

The growing number of elderly individuals presents new challenges for society. Many elderly individuals have physical or cognitive impairments and require support from caregivers. An attempt to overcome the limitations caused by the lack of human caregivers is the inclusion of assistive technology such as socially active robots. The Domeo-project of the Ambient Assisted Living Joint Programme of the European Union aims to develop a new companion robotic system that would allow assistance to the elderly. The requirements and attitude of the potential users and caregivers have been assessed in Austria, France and Hungary. The robot functions were demonstrated to the participants. Three focus groups were formed: potential end users, older caregivers and younger caregivers. The discussions were recorded and processed according to six aspects: (i) acceptability and privacy, (ii) pertinence of services, (iii) possible obstacles, (iv) motivation level to use the proposed services, (v) organizational issues and (vi) recommendations. Minor differences were observed between the countries, but there were considerable differences regarding the age of the participants. The younger caregivers want to be assured of the safety of their client and to receive immediate notification in case of an emergency. As for the elderly, the most important aspect is to gain a companion and a physical helper. Many of the recommendations can be taken into consideration during robot development, but some of them are not realistic at present.
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http://dx.doi.org/10.1097/MRR.0b013e3283643d26DOI Listing
December 2013

Identification of 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (setipiprant/ACT-129968), a potent, selective, and orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist.

J Med Chem 2013 Jun 13;56(12):4899-911. Epub 2013 Jun 13.

Drug Discovery Unit, Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.

Herein we describe the discovery of the novel CRTh2 antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 28 (setipiprant/ACT-129968), a clinical development candidate for the treatment of asthma and seasonal allergic rhinitis. A lead optimization program was started based on the discovery of the recently disclosed CRTh2 antagonist 2-(2-benzoyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 5. An already favorable and druglike profile could be assessed for lead compound 5. Therefore, the lead optimization program mainly focused on the improvement in potency and oral bioavailability. Data of newly synthesized analogs were collected from in vitro pharmacological, physicochemical, in vitro ADME, and in vivo pharmacokinetic studies in the rat and the dog. The data were then analyzed using a traffic light selection tool as a visualization device in order to evaluate and prioritize candidates displaying a balanced overall profile. This data-driven process and the excellent results of the PK study in the rat (F = 44%) and the dog (F = 55%) facilitated the identification of 28 as a potent (IC50 = 6 nM), selective, and orally available CRTh2 antagonist.
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http://dx.doi.org/10.1021/jm400122fDOI Listing
June 2013

Assessment of the frequency of different Borrelia burgdorferi sensu lato species in patients with Lyme borreliosis from north-east Poland by studying preferential serologic response and DNA isolates.

Ann Agric Environ Med 2013 ;20(1):21-9

Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, Poland.

Introduction And Objective: Several Borrelia burgdorferi sensu lato species cause Lyme borreliosis throughout Europe and their geographic distribution may influence clinical manifestations of the disease. In Poland, Lyme borreliosis presents mainly with neurologic and cutaneous symptoms, while clinically overt arthritis is rare. The presented study investigates the prevalence of B. burgdorferi s.l. genospecies in a group of patients with different clinical forms and stages of Lyme borreliosis in north-east of Poland. This has not previously been studied.

Material And Methods: Preferential reactivity towards different B.burgdorferi s.l. species was investigated with a previously validated immunoblot assay in sera of 33 patients with disseminated Lyme borreliosis: 10 with neuroborreliosis, 6 with acrodermatitis chronica atrophicans and 17 with osteoarticular symptoms. Also typed were B.burgdorferi s.l. DNA isolated from the skin and synovial fluid of 7 patients with erythema migrans, acrodermatitis chronic atrophicans and arthritis.

Results: Preferential reactivity was detected in 30 out of 33 serum samples. Of these, 25 reacted preferentially with B.afzelii, 3 with B. garinii and 2 with B. burgdorferi ss. B.burgdorferi DNA was isolated from all studied samples and typed as B.afzelii in 5. In a patient with acrodermatitis chronica atrophicans studied with both methods simultaneously, B.afzelii was identified by both genotyping and serotyping.

Conclusions: Both methods gave consistent results, indicating B.afzelii as the main agent of all the clinical forms of the Lyme borreliosis in the study area.
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September 2013

Point-of-admission hypoglycaemia among under-five Nigerian children with plasmodium falciparum malaria: prevalence and risk factors.

Med J Islam Repub Iran 2012 May;26(2):78-84

MD. Department of Child Health, University of Benin Teaching Hospital, Pmb 1111, Benin City, Nigeria.

Background: Hypoglycaemia is a well recognized complication of falciparum malaria in children but its diagnosis may be overlooked because all the clinical features may be mimicked by severe malaria. To determine the prevalence of hypoglycaemia at the point of hospital admission of under-fives with falciparum malaria and identify its risk factors in patients seen in a Nigerian secondary-health-care institution.

Methods: During a 12-month period and at the point of hospital admission, venous blood sample was collected into an appropriate sample bottle (fluoride-oxalate bottle) from 502 children who were below 5 years of age with positive falciparum malaria parasitaemia. The blood sample was analysed using the glucose-oxidase method. The duration of illness, degree of parasitaemia and time of last meal were noted for each child.

Results: Ninety two (18.3%) out of 502 children below five years old with falciparum malaria had hypoglycaemia ( blood glucose below 2.6 mmol/L or 50 mg/dl) at the point of hospital admission. Twenty three percent (78 out of 339) of children below 36 months old were hypoglycaemic compared to 8.6% (14 out of 163) children aged 36 months and above; (p=0.01). Prevalence of hypoglycaemia was higher in girls (20.7%) than boys (16.3%) [Odd ratio, OR=0.75 (95% Confidence Interval, CI=0.48-1.18)]. Forty (13.1%) out of 305 children whose time of last meal was 12 hours and below had hypoglycaemia compared to 52(26.4%) out of 197 whose time of last meal was greater than 12 hours; (p=0.02). Hypoglycaemia at admission point was associated with a significant increase in mortality rate; (p=0.00). The duration of illness and the degree of parasitaemia did not have significant difference with the prevalence of hypoglycaemia.

Conclusion: In falciparum malaria, a greater interval (between 2 meals) than 12 hours in children below 36 months old predisposed them to hypoglycaemia. Routine monitoring of blood glucose at the admission point is suggested in malaria endemic region.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587904PMC
May 2012

Evolution of novel tricyclic CRTh2 receptor antagonists from a (E)-2-cyano-3-(1H-indol-3-yl)acrylamide scaffold.

Bioorg Med Chem Lett 2013 Feb 25;23(4):944-8. Epub 2012 Dec 25.

Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil, Switzerland.

(E)-2-(3-(3-((3-Bromophenyl)amino)-2-cyano-3-oxoprop-1-en-1-yl)-1H-indol-1-yl)acetic acid (1) was discovered in a HTS campaign for CRTh2 receptor antagonists. An SAR around this hit could be established and representatives with interesting activity profiles were obtained. Ring closing tactics to convert this hit series into a novel 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole based CRTh2 receptor antagonist series is presented.
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http://dx.doi.org/10.1016/j.bmcl.2012.12.050DOI Listing
February 2013

Tick related diseases in Switzerland, 2008 to 2011.

Swiss Med Wkly 2013 8;143:w13725. Epub 2013 Jan 8.

Federal Office of Public Health,Bern, Switzerland.

Question Under Study: To determine the incidence and determinants of tick related diseases in Switzerland, for example tick bites and Lyme borreliosis in primary care and tick borne encephalitis.

Methods: Analysis of the Swiss data collected by mandatory and facultative surveillance systems for the reporting period of 2008 to 2011.

Results: Tick related diseases in Switzerland are common. About 17,000 to 23,000 estimated cases of tick bites lead to a consultation (yearly incidence 254 per 100,000 inhabitants); about 7,000 to 12,000 estimated cases of Lyme borreliosis (yearly incidence 131 per 100,000 inhabitants) and 98 to 172 cases of tick borne encephalitis occur each year (yearly incidence 1.6 per 100,000 inhabitants). The most affected area is the north-eastern part of Switzerland. Whereas cases of tick borne encephalitis are restricted to local endemic areas, cases of Lyme borreliosis and tick bites are spread all over Switzerland.

Conclusions: Tick related diseases are frequent and widespread in Switzerland. They are leading to a considerable usage of the health care system. Thus, tick bite prevention and vaccination against tick borne encephalitis are essential. However, long term follow-up cohort studies with reasonably large study populations after tick bite would be required to elucidate the risk of developing a tick borne disease.
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http://dx.doi.org/10.4414/smw.2013.13725DOI Listing
June 2013

[Q fever: a cause of fever of unknown origin in Switzerland].

Rev Med Suisse 2012 Oct;8(357):1921-4

Service de médecine, Hôpital du Chablais, Route de Morgins, 1870 Monthey.

We describe two cases of Q fever in previously healthy women presenting with fever of unknown origin. The diagnosis was made after several days of investigations. Symptoms and signs of acute or chronic Coxiella burnetii infection are protean and non-specific. Q fever should be included in the differential diagnosis of fever of unknown origin and appropriate serologic studies should be done. We review the clinical presentation of Q fever. Use of serology for the diagnosis and the follow-up is discussed.
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October 2012
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