Publications by authors named "Joseph O"

42 Publications

Cerebral Air Embolism After Gastrointestinal Procedure: A Case Report and Literature Review.

J Med Cases 2021 Mar 19;12(3):119-125. Epub 2021 Jan 19.

Department of Medical Education, Saint Michael's Medical Centre, New York Medical College, Newark, NJ, USA.

Esophagogastroduodenoscopy (EGD) is one of the forefronts of minimally invasive modalities with excellent safety records and tremendous capability but despite its accolades and functions, there are still very rare complications including air embolism. It is a life-threatening condition that could lead to a significant increase in morbidity and mortality. However, there are limited data for incidence of air embolism in association with gastrointestinal endoscopy. Diagnosis of air embolism after or during gastrointestinal endoscopy might be a difficult task due to overlapping presentations with anesthesia effects on the cardiopulmonary and the neurological systems, as a result, there should be increased awareness allowing clinicians to quickly rule out air embolism in patient with altered mental status or cardiopulmonary changes after or during gastrointestinal endoscopy. Herein, we report a unique case of cerebral air embolism after EGD in a 79-year-old female patient. In addition, we also performed a systematic review of cases based on PRISMA guideline, with the aim to investigate the demographics and clinical outcomes associated with this complication. This systematic review of cases hopes to increase the awareness about this rare entity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14740/jmc3639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383579PMC
March 2021

"We are not hard to reach, but we may find it hard to trust" …. Involving and engaging 'seldom listened to' community voices in clinical translational health research: a social innovation approach.

Res Involv Engagem 2021 Jun 26;7(1):46. Epub 2021 Jun 26.

Public Programmes Team (now Vocal), Manchester University NHS Foundation Trust, Research & Innovation Division, The Nowgen Centre, 29 Grafton Street, Manchester, M13 9WU, UK.

Background: Public involvement in clinical translational research is increasingly recognised as essential for relevant and reliable research. Public involvement must be diverse and inclusive to enable research that has the potential to reach those that stand to benefit from it the most, and thus address issues of health equity. Several recent reports, however, indicate that public involvement is exclusive, including in its interactions with ethnic groups. This paper outlines a novel community-led methodology - a community sandpit - to address the inclusion of ethnic groups in public involvement in research, reports on its evaluation, findings, legacy and impact.

Methods: Through detailed planning - thinking through and taking into account all stakeholders perspectives in the planning and design of the sandpit, relationship-building, co-design and co-delivery between the Public Programmes team based at Manchester University NHS Foundation Trust and the Greater Manchester Black and Minority Ethnic Network - the community sandpit was held in July 2018.

Results: Fifteen community organisations took part in the two-day event, as well as six researchers, and six creative practitioners. Six community-based partnership projects were seed-funded; four of these received additional funding from other sources also.

Conclusions: Evaluation of the sandpit showed the format to be well-received by all: it levelled power relationships between community organisations, health researchers and research infrastructure; it developed capacity amongst researchers about the accessibility, role and potential of community organisations. Described as "not another community seed fund" by community partners, the sandpit offered community partners, equitable avenues for collaboration within Greater Manchester translational research and led to the formation of the Black, Asian and Minority Ethnic Research Advisory Group (BRAG Vocal Website information, - https://www.wearevocal.org/opportunities/black-asian-and-minority-ethnic-research-advisory-group-brag/ , 2021). The method has the potential to be replicated elsewhere to support inclusive public involvement in research and inclusive research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40900-021-00292-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234650PMC
June 2021

Challenging Airway Management in a Patient with Retrosternal Goiter Presenting in Respiratory Distress.

Niger J Surg 2021 Jan-Jun;27(1):66-70. Epub 2021 Mar 9.

Department of Anaesthesia, University College Hospital, Ibadan, Nigeria.

A number of options exist for patients with anticipated difficult intubation on account of a retrosternal goiter compressing on the trachea. The chosen technique(s) to secure the airway in this delicate situation often depends on the location and degree of airway obstruction, available resources/facilities, and an anesthetist's experience and preferences. We report the case of a 68-year-old woman with severe airway obstruction from a retrosternal goiter coming for total thyroidectomy. Airway management started with an awake fiber-optic intubation, proceeded to a tracheostomy and finally to use of a rigid bronchoscope following failure of the earlier techniques to achieve adequate ventilation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/njs.NJS_58_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112356PMC
March 2021

Marantic Endocarditis Associated with COVID-19: A Rare Case Report of a Potentially Deadly Disease.

Eur J Case Rep Intern Med 2021 19;8(3):002409. Epub 2021 Mar 19.

Department of Medical Education, Saint Michael's Medical Centre, New York Medical College, Newark, New Jersey, USA.

Coronavirus disease 2019 (COVID-19) has overwhelmed healthcare globally with millions of cases and over 2 million deaths worldwide. The hypercoagulable state associated with COVID-19 is a well-recognized complication that carries a poor prognosis. Marantic endocarditis, or non-bacterial thrombotic endocarditis (NBTE), is caused by a sterile vegetation on the cardiac valves resulting from the deposition of fibrin and platelet aggregates. It is highly associated with the hypercoagulable and acquired inflammatory states. Herein, we report a unique and rare case of COVID-19 presenting with NBTE.

Learning Points: COVID-19 has caused a major global pandemic, with high morbidity and mortality.One of the complications of COVID-19 infection is a hypercoagulable state.To the best of our knowledge, we present only the second case of marantic endocarditis in a patient with COVID-19, in the hope of raising awareness among physicians of this potential rare association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12890/2021_002409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046274PMC
March 2021

Segment-Specific Orientation of the Dorsal and Ventral Roots for Precise Therapeutic Targeting of Human Spinal Cord.

Mayo Clin Proc 2021 06 5;96(6):1426-1437. Epub 2021 Mar 5.

Department of Neurology, Mayo Clinic, Rochester, MN; Kazan Federal University, Kazan, Russia; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN. Electronic address:

Objective: To provide precise description of the dorsal and ventral roots orientation along with the main spinal cord anatomical measurements and their segment-specific variations.

Patients And Methods: We collected and analyzed the measurements of the spines, spinal cords, and dorsal and ventral roots (C2-L5) of nine adult cadavers (five males and four females).

Results: This study for the first time provides analysis of the dorsal and ventral roots orientation along with spinal cord anatomical measurements and their segment-specific distribution. The results of this study showed less variability in rostral root angles compared with the caudal. Dorsal and ventral rootlets were oriented mostly perpendicular to the spinal cord at the cervical level and had more parallel orientation to the spinal cord at the thoracic and lumbar segments. The number of rootlets per root was greatest at dorsal cervical and lumbar segments. Spinal cord transverse diameter and width of the dorsal columns were largest at cervical segments. The strongest correlation between the spinal cord and vertebrae structures was found between the length of intervertebral foramen to rostral rootlet distance and vertebral bone length.

Conclusion: These results demonstrate consistent variation in spinal cord anatomical features across all tested subjects. The results of this study can be used to locate spinal roots and main spinal cord landmarks based on bone marks on computed tomography or X-rays. These results could improve stereotactic surgical procedures and electrode positioning for neuromodulation procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2020.07.039DOI Listing
June 2021

Role of silicon in the development of complex crystal shapes in coccolithophores.

New Phytol 2021 09 9;231(5):1845-1857. Epub 2021 Mar 9.

Marine Biological Association, The Laboratory, Citadel Hill, Plymouth, PL1 2PB, UK.

The development of calcification by the coccolithophores had a profound impact on ocean carbon cycling, but the evolutionary steps leading to the formation of these complex biomineralized structures are not clear. Heterococcoliths consisting of intricately shaped calcite crystals are formed intracellularly by the diploid life cycle phase. Holococcoliths consisting of simple rhombic crystals can be produced by the haploid life cycle stage but are thought to be formed extracellularly, representing an independent evolutionary origin of calcification. We use advanced microscopy techniques to determine the nature of coccolith formation and complex crystal formation in coccolithophore life cycle stages. We find that holococcoliths are formed in intracellular compartments in a similar manner to heterococcoliths. However, we show that silicon is not required for holococcolith formation and that the requirement for silicon in certain coccolithophore species relates specifically to the process of crystal morphogenesis in heterococcoliths. We therefore propose an evolutionary scheme in which the lower complexity holococcoliths represent an ancestral form of calcification in coccolithophores. The subsequent recruitment of a silicon-dependent mechanism for crystal morphogenesis in the diploid life cycle stage led to the emergence of the intricately shaped heterococcoliths, enabling the formation of the elaborate coccospheres that underpin the ecological success of coccolithophores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nph.17230DOI Listing
September 2021

Patient and Public Involvement Refines the Design of ProtOeus: A Proposed Phase II Trial of Proton Beam Therapy in Oesophageal Cancer.

Patient 2021 Sep 23;14(5):545-553. Epub 2020 Dec 23.

CRUK MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.

Background: Neoadjuvant chemoradiotherapy for oesophageal cancer significantly improves overall survival but is associated with severe post-operative complications. Proton beam therapy may reduce these toxicities by sparing normal tissues compared with standard radiotherapy. ProtOeus is a proposed randomised phase II study of neoadjuvant chemoradiotherapy in oesophageal cancer that compares proton beam therapy to standard radiotherapy techniques. As proton beam therapy services are often centralised in academic centres in major cities, proton beam therapy trials raise distinct challenges including patient acceptance of travelling for proton beam therapy, coordination of treatments with local centres and ensuring equity of access for patients.

Methods: Focus groups were held early in the trial development process to establish patients' views on the trial proposal. Topics discussed include perception of proton beam therapy, patient acceptability of the trial pathway and design, patient-facing materials, and common clinical scenarios. Focus groups were led by the investigators and facilitated by patient involvement teams from the institutions who are involved in this research. Responses for each topic were analysed, and fed back to the trial's development group.

Results: Three focus groups were held in separate locations in the UK (Manchester, Cardiff, Wigan). Proton beam therapy was perceived as superior to standard radiotherapy making the trial attractive. Patients felt strongly that travel costs should be reimbursed to ensure equity of access to proton beam therapy. They were very supportive of a shorter treatment schedule and felt that toxicity reduction was the most important endpoint.

Discussion And Conclusions: Incorporating patient views early in the trial development process resulted in significant trial design refinements including travel/accommodation provisions, choice of primary endpoint, randomisation ratio and fractionation schedule. Focus groups are a reproducible and efficient method of incorporating the patient and public voice into research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40271-020-00487-8DOI Listing
September 2021

Morphological investigation and mechanical behaviour of agrowaste reinforced aluminium alloy 8011 for service life improvement.

Heliyon 2020 Nov 16;6(11):e05506. Epub 2020 Nov 16.

Mechanical Engineering Department, University of Johannesburg, South Africa.

Aluminium composite materials are beneficial in most engineering applications, most notably, because of their lightweight to strength ratio amongst many others. This study reports the reinforcement of aluminium alloy 8011 with cow horn and corncob in varying weight percentages of 5wt%, 10wt%, 15wt% and 20wt%. This study adopted the Stir casting method based on availability and cost-effectiveness as the cheapest method amongst others. The developed composite materials were in eight different samples alongside one control sample of the aluminium alloy base material. The samples used for this experimental study were tested for tensile strength, hardness and microstructural analysis. The outcome of the study shows that the sample with 20wt% of cow horn reinforcement gave the best-improved properties in terms of yield strength, ultimate tensile strength (UTS) and hardness with percentage improvement of 57%, 52.6% and 54.4% respectively. Hardness was also improved with 52.6% over the control sample with the 15wt% cow horn reinforced sample. Cow horn of 10wt% reinforcement improved the material by 61%. The results shown have justified the relevant effect of agro-waste materials in composite development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2020.e05506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679252PMC
November 2020

Dataset on corrosion degradation behaviour of mild steel in developed nano-cutting coolant from agro waste.

Data Brief 2020 Dec 21;33:106435. Epub 2020 Oct 21.

Department of Physics, Covenant University, Ota, Nigeria.

Investigation of the corrosion degradation behaviour of mild steel in an admixture of coconut shell and egg shell (CS-ES) based nano-fluid was presented in this study. Mild steel coupons were immersed in different concentrations (nine concentrations and the control as a reference) of the developed nano-fluid for a period of 24, 48, 72, 96, 120, 144 and 168 h. Corrosion rate was calculated based on ASTM Standard G1-03 standard practice for preparing, cleaning and evaluation of corrosion test specimens. Open circuit potential measurements (OCP) were also carried out. The potential of the steel samples in the nano-fluid with respect to time was investigated. This dataset could be used in evaluating the performance of mild steel in CS-ES based nano-fluid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2020.106435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599424PMC
December 2020

Inhibitory potentials of oil against aluminium-induced behavioral deficits and neuropathology in rats.

Anat Cell Biol 2020 Sep;53(3):342-354

Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.

is a tropical phytomedicinal plant that is widely known for its hypoglycemic, hypolipidemic, anxiolytic, sedative, antioxidative and anti-inflammatory properties. In this study, we have examined the neuroprotective effects of the essential oil (ESO) of , following aluminum chloride (AlCl)-induced neurotoxicity within the cerebellum of Wistar rats. A total of 40 adult male Wistar rats were assigned into five groups and treated orally as follows: A-phosphate-buffered saline (1 ml daily for 15 days); B-ESO (50 mg/kg daily for 15 days); C-AlCl (100 mg/kg daily for 15 days); D-AlCl then ESO (100 mg/kg AlCl daily for 15 days followed by 50 mg/kg ESO daily for subsequent 15 days); E-ESO then AlCl (50 mg/kg ESO daily for 15 days followed by 100 mg/kg AlCl daily for following 15 days). To address our questions, we observed the locomotion and exploratory behavior of the rats in the open field apparatus and subsequently evaluated cerebellar oxidative redox parameters, neural bioenergetics, acetylcholinesterase levels, transferrin receptor protein, and total protein profiles by biochemical assays. Furthermore, we investigated cerebellar histomorphology and Nissl profile by H&E and Cresyl violet Nissl staining procedures. ESO treatment markedly attenuated deficits in exploratory activities and rearing behavior following AlCl toxicity, indicating its anxiolytic potentials. Additionally, AlCl evokedincrease in malondialdehyde and nitric oxide levels, as well as repressed cerebellar catalase, glutathione peroxidase, and superoxide dismutase profiles were normalised to baseline levels by ESO treatment. Treatment with ESO, ergo, exhibits substantial neuroprotective and modulatory potentials in response to AlCl toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5115/acb.20.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527123PMC
September 2020

Seed dispersal of wild radishes and its association with within-population spatial distribution.

BMC Ecol 2020 05 11;20(1):30. Epub 2020 May 11.

Institute of Plant Sciences, Agricultural Research Organization, 7505101, Rishon LeZion, Israel.

Background: The wild radishes, Raphanus raphanistrum and R. pugioniformis (Brassicaceae) are native to the East Mediterranean region. However, whereas R. raphanistrum is widely distributed worldwide, the endemic R. pugioniformis is limited to specific habitats. In R. raphanistrum the diaspores of the indehiscent fruits comprise glabrous, light, single-seeded segments, whereas the intact fruits of R. pugioniformis are heavy and covered with spiny backward-pointing trichomes. We aimed to investigate whether the structure of the diaspores was directly associated with long- and short-range dispersal in R. raphanistrum and R. pugioniformis, respectively. We further surveyed within-population spatial distributions, to test the hypothesis that short- and long-range dispersal contribute to a patchy vs. uniform distribution patterns of R. pugioniformis and R. raphanistrum, respectively.

Results: The results indicated that dispersal by wind and run-off water was substantially lower for diaspores of R. pugioniformis than for those of R. raphanistrum diaspores. Supporting the hypothesis that backward-pointing trichomes promote adherence to soil particles, the displacement on soil surface of R. pugioniformis fruits depended on their orientation relative to wind direction. Furthermore, trichome removal from fruits of R. pugioniformis significantly reduced wind velocity needed to remove fruits that were placed on soils typical of the species' natural habitats. The spatial-distribution survey results indicated a patchy distribution of R. pugioniformis populations as compared with the more uniform arrangement in the studied populations of R. raphanistrum; consistent with the unidirectional vs. homogeneous wind dispersal of the respective diaspores, with respect to wind direction. In addition, R. pugioniformis population sizes changed less between years than those of R. raphanistrum.

Conclusions: Overall, our results indicate that fruit structure is strongly linked to dispersal ability and spatial distribution of the two closely related wild radish species. Whereas R. raphanistrum inhabits homogenous sandy soil habitats, the distribution range of R. pugioniformis includes heterogeneous environments in which growth niches are scarcer. We suggest that the different modes of dispersal have evolved as adaptive traits appropriate to the species' specific habitats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12898-020-00297-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212605PMC
May 2020

Assessing the Feasibility of Adapting a School-Based HIV Prevention Intervention to Include Voluntary Male Medical Circumcision and Vaccination for Human Papilloma Virus Prevention.

East Afr Health Res J 2020 26;4(1):108-112. Epub 2020 Jun 26.

Kenya Medical Research Institute Centre for Global Health Research, Kisumu, Kenya.

In 2012, there were 2,454 cases and 1,676 deaths from cervical cancer in Kenya. Human Papilloma Virus (HPV) is responsible for 99% of all cervical cancers. National cervical cancer prevention guidelines recommend HPV vaccination among HPV-naïve pre-adolescent girls' prior to onset of sexual activity preferably through school-based interventions. Similarly, Voluntary Male Medical Circumcision (VMMC) programs also reduce sexually transmitted infections like HIV, and ideally should also be conducted prior to the onset of sexual activity. The Families Matter! Program (FMP) is a school-based evidence-based HIV prevention intervention for parents and guardians of pre-adolescents aimed to enhance protective parenting practices in order to reduced sexual risk-taking among adolescents. In this paper we describe how we will recruit a cohort of 55 parent-child dyads in a primary school in Kisumu County then implement and evaluate an adapted FMP program that incorporates VMMC promotion and HPV vaccination in conjunction. It is anticipated that the intervention will enhance parental-child communication about sexual matters, promote safe sexual practices and uptake of biomedical prevention interventions and overall reproductive health among the pre-adolescents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.24248/eahrj.v4i1.628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279225PMC
June 2020

Innovating public engagement and patient involvement through strategic collaboration and practice.

Res Involv Engagem 2019 21;5:30. Epub 2019 Oct 21.

Public Programmes Team, Manchester University NHS Foundation Trust, The Nowgen Centre, 29 Grafton Street, Manchester, M13 9WU England.

Background: Patient and public involvement and engagement is an important and expected component of health-related research activity in the UK. Specifically within the health research sphere, public engagement (usually defined as raising awareness of research) and patient involvement (usually defined as actively involving people in research) have traditionally been seen as separate but have much to gain from working together towards a common goal of better health outcomes for all.

Methods: This paper describes a unique approach taken by the Public Programmes Team: a small interdisciplinary team of public engagement specialists, with backgrounds in science, community development, public engagement and involvement, policy, ethics, communications, industry, museums and creative practice, embedded within translational research infrastructure and delivery in Manchester in the North West of England. We propose a new model of professional practice - a 'cycle' of engagement and involvement - innovating across the complementary fields of public engagement and patient involvement, and working inclusively and in partnership with people in health research. Further, our approach capitalises on strategic collaboration offering economies of scale and a joined up way of working. Our ambition is to boldly experiment, learn and reflect, responsibly and based on evidence and partnerships, using methods of engagement that address issues of social justice.

Results: Here, we report on preliminary case studies exemplifying the impact of our approach, and data relating to achievements and learning between April 2017 and March 2018. Informed by our findings, we propose that our approach has the potential to be replicated elsewhere.

Conclusions: Our practice and the beginning of its evaluation lead us to believe that our way of working and model of professional practice - the 'cycle' of engagement and involvement - is effective in: addressing our vision of making health research relevant and inclusive for everyone; and embedding and joining up public involvement in a busy and fertile translational health research ecosystem.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40900-019-0160-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802177PMC
October 2019

Identification of Fatty Acid Binding Protein 5 Inhibitors Through Similarity-Based Screening.

Biochemistry 2019 10 11;58(42):4304-4316. Epub 2019 Oct 11.

Department of Applied Mathematics & Statistics , Stony Brook University , Stony Brook , New York 11794 , United States.

Fatty acid binding protein 5 (FABP5) is a promising target for development of inhibitors to help control pain and inflammation. In this work, computer-based docking (DOCK6 program) was employed to screen ∼2 M commercially available compounds to FABP5 based on an X-ray structure complexed with the small molecule inhibitor SBFI-26 previously identified by our group (also through virtual screening). The goal was discovery of additional chemotypes. The screen resulted in the purchase of 78 candidates, which led to the identification of a new inhibitor scaffold (STK-0) with micromolar affinity and apparent selectivity for FABP5 over FABP3. A second similarity-based screen resulted in three additional hits (STK-15, STK-21, STK-22) from which preliminary SAR could be derived. Notably, STK-15 showed comparable activity to the SBFI-26 reference under the same assay conditions (1.40 vs 0.86 μM). Additional molecular dynamics simulations, free energy calculations, and structural analysis (starting from DOCK-generated poses) revealed that R enantiomers (dihydropyrrole scaffold) of STK-15 and STK-22 have a more optimal composition of functional groups to facilitate additional H-bonds with Arg109 of FABP5. This observation suggests enantiomerically pure compounds could show enhanced activity. Overall, our study highlights the utility of using similarity-based screening methods to discover new inhibitor chemotypes, and the identified FABP5 hits provide a strong starting point for future efforts geared to improve activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.biochem.9b00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812325PMC
October 2019

FABP1 controls hepatic transport and biotransformation of Δ-THC.

Sci Rep 2019 05 20;9(1):7588. Epub 2019 May 20.

Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York, 11794, USA.

The increasing use of medical marijuana highlights the importance of developing a better understanding of cannabinoid metabolism. Phytocannabinoids, including ∆-tetrahydrocannabinol (THC), are metabolized and inactivated by cytochrome P450 enzymes primarily within the liver. The lipophilic nature of cannabinoids necessitates mechanism(s) to facilitate their intracellular transport to metabolic enzymes. Here, we test the central hypothesis that liver-type fatty acid binding protein (FABP1) mediates phytocannabinoid transport and subsequent inactivation. Using X-ray crystallography, molecular modeling, and in vitro binding approaches we demonstrate that FABP1 accommodates one molecule of THC within its ligand binding pocket. Consistent with its role as a THC carrier, biotransformation of THC was reduced in primary hepatocytes obtained from FABP1-knockout (FABP1-KO) mice. Compared to their wild-type littermates, administration of THC to male and female FABP1-KO mice potentiated the physiological and behavioral effects of THC. The stark pharmacodynamic differences were confirmed upon pharmacokinetic analyses which revealed that FABP1-KO mice exhibit reduced rates of THC biotransformation. Collectively, these data position FABP1 as a hepatic THC transport protein and a critical mediator of cannabinoid inactivation. Since commonly used medications bind to FABP1 with comparable affinities to THC, our results further suggest that FABP1 could serve a previously unrecognized site of drug-drug interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-44108-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527858PMC
May 2019

Molecular Docking and 3D Qsar Studies of C000000956 as a Potent Inhibitor of Bace-1.

Drug Res (Stuttg) 2019 Aug 19;69(8):451-457. Epub 2019 Feb 19.

Centre for Biocomputing and Drug Development, Adekunle Ajasin University, Akungba Akoko, Ondo State Nigeria.

Background: BACE-1 is an aspartate protease that is responsible for the proteolysis of amyloid precursor proteins (APP) into beta-amyloid (Aβ), a neurotoxic peptide in patients with Alzheimer's disease (AD). As such, BACE-1 is a prime pharmacological target in the control of Aβ in the brain and its inhibition will be a sound approach in AD therapy.

Methods: The computational pipeline which comprised molecular docking (MD), Quantitative Structure Activity Relationship (QSAR) modelling and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) studies enabled the prediction of molecular interaction and relative inhibitory potentials of the hit compound.

Results And Discussion: The current study reports a naturally sourced small molecule inhibitor of BACE1 (C000000956) which was obtained through a computational pipeline. Also, pharmacological constraints such as pH dependent activity of the enzyme and blood brain barrier permeation which have been associated with the efficacy of previous BACE-1 inhibitors were well catered for. Our results suggest that orally delivered C000000956 is a potential small molecule inhibitor of BACE-1 which may find usefulness in AD-therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-0849-9377DOI Listing
August 2019

Knowledge, attitudes and practices of West Africans on genetic studies of stroke: Evidence from the SIREN Study.

Int J Stroke 2019 01 24;14(1):69-79. Epub 2018 Jul 24.

7 Aminu Kano Teaching Hospital, Bayero University, Kano, Nigeria.

Background: It is crucial to assess genomic literacy related to stroke among Africans in preparation for the ethical, legal and societal implications of the genetic revolution which has begun in Africa.

Objective: To assess the knowledge, attitudes and practices (KAP) of West Africans about stroke genetic studies.

Methods: A comparative cross-sectional study was conducted among stroke patients and stroke-free controls recruited across 15 sites in Ghana and Nigeria. Participants' knowledge of heritability of stroke, willingness to undergo genetic testing and perception of the potential benefits of stroke genetic research were assessed using interviewer-administered questionnaire. Descriptive, frequency distribution and multiple regression analyses were performed.

Results: Only 49% of 2029 stroke patients and 57% of 2603 stroke-free individuals knew that stroke was a heritable disorder. Among those who knew, 90% were willing to undergo genetic testing. Knowledge of stroke heritability was associated with having at least post-secondary education (OR 1.51, 1.25-1.81) and a family history of stroke (OR 1.20, 1.03-1.39) while Islamic religion (OR=0.82, CI: 0.72-0.94), being currently unmarried (OR = 0.81, CI: 0.70-0.92), and alcohol use (OR = 0.78, CI: 0.67-0.91) were associated with lower odds of awareness of stroke as a heritable disorder. Willingness to undergo genetic testing for stroke was associated with having a family history of stroke (OR 1.34, 1.03-1.74) but inversely associated with a medical history of high blood pressure (OR = 0.79, 0.65-0.96).

Conclusion: To further improve knowledge of stroke heritability and willingness to embrace genetic testing for stroke, individuals with less formal education, history of high blood pressure and no family history of stroke require targeted interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493018790059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325169PMC
January 2019

SAR studies on truxillic acid mono esters as a new class of antinociceptive agents targeting fatty acid binding proteins.

Eur J Med Chem 2018 Jun 26;154:233-252. Epub 2018 May 26.

Department of Chemistry, Stony Brook University, Stony Brook, NY, 11794-3400, United states; Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, 11794-3400, United states. Electronic address:

Fatty acid binding proteins (FABPs) serve as critical modulators of endocannabinoid signaling by facilitating the intracellular transport of anandamide and whose inhibition potentiates anandamide signaling. Our previous work has identified a novel small-molecule FABP inhibitor, α-truxillic acid 1-naphthyl monoester (SB-FI-26, 3) that has shown efficacy as an antinociceptive and anti-inflammatory agent in rodent models. In the present work, we have performed an extensive SAR study on a series of 3-analogs as novel FABP inhibitors based on computer-aided inhibitor drug design and docking analysis, chemical synthesis and biological evaluations. The prediction of binding affinity of these analogs to target FABP3, 5 and 7 isoforms was performed using the AutoDock 4.2 program, using the recently determined co-crystal structures of 3 with FABP5 and FABP7. The compounds with high docking scores were synthesized and evaluated for their activities using a fluorescence displacement assay against FABP3, 5 and 7. During lead optimization, compound 3l emerged as a promising compound with the Ki value of 0.21 μM for FABP 5, 4-fold more potent than 3 (Ki, 0.81 μM). Nine compounds exhibit similar or better binding affinity than 3, including compounds 4b (Ki, 0.55 μM) and 4e (Ki, 0.68 μM). Twelve compounds are selective for FABP5 and 7 with >10 μM Ki values for FABP3, indicating a safe profile to avoid potential cardiotoxicity concerns. Compounds 4f, 4j and 4k showed excellent selectivity for FABP5 and would serve as other new lead compounds. Compound 3a possessed high affinity and high selectivity for FABP7. Compounds with moderate to high affinity for FABP5 displayed antinociceptive effects in mice while compounds with low FABP5 affinity lacked in vivo efficacy. In vivo pain model studies in mice revealed that exceeding hydrophobicity significantly affects the efficacy. Thus, among the compounds with high affinity to FABP5 in vitro, the compounds with moderate hydrophobicity were identified as promising new lead compounds for the next round of optimization, including compounds 4b and 4j. For select cases, computational analysis of the observed SAR, especially the selectivity of new inhibitors to particular FABP isoforms, by comparing docking poses, interaction map, and docking energy scores has provided useful insights.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2018.04.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999033PMC
June 2018

Predictive value of Pirani scoring system for tenotomy in the management of idiopathic clubfoot.

J Orthop Surg (Hong Kong) 2017 May-Aug;25(2):2309499017713896

3 Department of Community Health, Obafemi Awolowo University, Ile-Ife, Nigeria.

Purpose: To determine the predictive value of the Pirani scoring system in the need for tenotomy using the Ponseti method for management of idiopathic clubfoot.

Method: This is a prospective observational study involving patients less than 2 years of age with idiopathic clubfoot. The consenting parents and institution ethical board approved the study. The relationship between Pirani scores and the need for tenotomy was evaluated using the independent t-test and the binary logistic regression to predict the need for tenotomy. Pearson's r and Cohen's κ were used to measure correlation and agreement, respectively, between the predicted and observed values. A receiver operating characteristic curve was used to interpret sensitivity and specificity levels as well as to obtain a cutoff score for predicting the requirement for tenotomy.

Results: Eighty-four clubfeet from 50 patients were studied. Thirty-eight feet (45%) had percutaneous tenotomy. The initial total Pirani and hindfoot scores were found to predict the need for tenotomy with the model for prediction being able to predict correctly in 72.6% and 75% of the time, respectively. A higher Pirani score was associated with higher odds of requiring tenotomy (OR = 4.402, p < 0.001) and total Pirani score above the cutoff point of 4.75 predicted the need for tenotomy.

Conclusion: The indication for tenotomy appears to be well predicted using the Pirani scoring system with the odds of requiring a tenotomy increasing by more than fourfold for every unit increase in Pirani score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2309499017713896DOI Listing
February 2018

Prevalence and Prognostic Features of ECG Abnormalities in Acute Stroke: Findings From the SIREN Study Among Africans.

Glob Heart 2017 06 14;12(2):99-105. Epub 2017 Mar 14.

University of Ghana Medical School, Accra, Ghana.

Background: Africa has a growing burden of stroke with associated high morbidity and a 3-year fatality rate of 84%. Cardiac disease contributes to stroke occurrence and outcomes, but the precise relationship of abnormalities as noted on a cheap and widely available test, the electrocardiogram (ECG), and acute stroke outcomes have not been previously characterized in Africans.

Objectives: The study assessed the prevalence and prognoses of various ECG abnormalities among African acute stroke patients encountered in a multisite, cross-national epidemiologic study.

Methods: We included 890 patients from Nigeria and Ghana with acute stroke who had 12-lead ECG recording within first 24 h of admission and stroke classified based on brain computed tomography scan or magnetic resonance imaging. Stroke severity at baseline was assessed using the Stroke Levity Scale (SLS), whereas 1-month outcome was assessed using the modified Rankin Scale (mRS).

Results: Patients' mean age was 58.4 ± 13.4 years, 490 were men (55%) and 400 were women (45%), 65.5% had ischemic stroke, and 85.4% had at least 1 ECG abnormality. Women were significantly more likely to have atrial fibrillation, or left ventricular hypertrophy with or without strain pattern. Compared to ischemic stroke patients, hemorrhagic stroke patients were less likely to have atrial fibrillation (1.0% vs. 6.7%; p = 0.002), but more likely to have left ventricular hypertrophy (64.4% vs. 51.4%; p = 0.004). Odds of severe disability or death at 1 month were higher with severe stroke (AOR: 2.25; 95% confidence interval: 1.44 to 3.50), or atrial enlargement (AOR: 1.45; 95% confidence interval: 1.04 to 2.02).

Conclusions: About 4 in 5 acute stroke patients in this African cohort had evidence of a baseline ECG abnormality, but presence of any atrial enlargement was the only independent ECG predictor of death or disability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gheart.2017.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582979PMC
June 2017

Is renal medullary carcinoma the seventh nephropathy in sickle cell disease? A multi-center Nigerian survey.

Afr Health Sci 2016 Jun;16(2):490-6

University of Nigeria Teaching Hospital, Enugu.

Introduction: Previous studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption.

Objective: To estimate the prevalence of RMC and describe other renal complications in SCD.

Materials And Methods: 14 physicians (haematologists and urologists) in 11 tertiary institutions across the country were collated from patients' case notes and hospital SCD registers.

Results: Of the 3,596 registered sickle patients, 2 (0.056%) had been diagnosed with RMC over a ten year period, thereby giving an estimated prevalence rate of 5.6 per 100,000. The most common renal complication reported by the attending physicians was chronic kidney disease (CKD). The frequency of routine renal screening for SCD patients varied widely between centres - most were done at diagnosis, annually or bi-annually.

Conclusion: The ten year prevalence of RMC in Nigerian SCD patients was determined to be 5.6 (estimated incidence of 0.56). RMC is not more common in SCD patients and therefore cannot be regarded as a "Seventh Sickle nephropathy". Most of the managing physicians reported that the commonest nephropathy observed in their SCD patients was chronic kidney disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4314/ahs.v16i2.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994564PMC
June 2016

Role of Chloride in the Corrosion and Fracture Behavior of Micro-Alloyed Steel in E80 Simulated Fuel Grade Ethanol Environment.

Materials (Basel) 2016 Jun 16;9(6). Epub 2016 Jun 16.

Materials Science and Technology Division, CSIR-National Metallurgical Laboratory, Jamshedpur 831007, India.

In this study, micro-alloyed steel (MAS) material normally used in the production of auto parts has been immersed in an E80 simulated fuel grade ethanol (SFGE) environment and its degradation mechanism in the presence of sodium chloride (NaCl) was evaluated. Corrosion behavior was determined through mass loss tests and electrochemical measurements with respect to a reference test in the absence of NaCl. Fracture behavior was determined via J-integral tests with three-point bend specimens at an ambient temperature of 27 °C. The mass loss of MAS increased in E80 with NaCl up to a concentration of 32 mg/L; beyond that threshold, the effect of increasing chloride was insignificant. MAS did not demonstrate distinct passivation behavior, as well as pitting potential with anodic polarization, in the range of the ethanol-chloride ratio. Chloride caused pitting in MAS. The fracture resistance of MAS reduced in E80 with increasing chloride. Crack tip blunting decreased with increasing chloride, thus accounting for the reduction in fracture toughness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma9060463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456821PMC
June 2016

Trend of invasive pneumococal disease (IPD) in a South Western, Nigerian hospital.

Pan Afr Med J 2016 28;23:140. Epub 2016 Mar 28.

Department of Microbiology, University of Port-Harcort, Nigeria.

The recent introduction of the Heptavalent-pneumococcal vaccine (PCV-7) by private pharmaceutical companies in Nigeria, has generated interest in invasive bacterial diseases particularly IPD. Our objective in this study is to investigate the trend and occurrence rate of IPD in Abeokuta, Nigeria. Suspected IPD cases were assessed from Jan 2010 to Dec 2010 for demographic and Microbiological characteristics. Bacterial isolations and antibiotics susceptibility testing followed standard bacteriological procedure. Overall 471 cases of probable IPD was assessed, with 21(4.5%) cases of suspected pneumonia, 109(23.1%) cases of suspected meningitis, and 341(72.4%) cases of suspected septicaemia. Confirmed IPD cases were 9 with 2 cases of meningitis, 3 cases of septicaemia and 4 cases of pneumonia. Age range distribution showed, high distribution of IPD cases among children >1 with 5(55.6%) there was a statistically significant difference in gender p< 0.05 (X2 test) with females recording a higher occurrence than males. We conclude by advocating for better detection methods against IPD meningitis cases, and continuous surveillance into the serotypes of streptococcus pneumonia as well inclusion of the PCV vaccine into our childhood immunization program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11604/pamj.2016.23.140.5635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885718PMC
February 2017

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Nat Genet 2015 Apr 2;47(4):367-372. Epub 2015 Mar 2.

Department of Radiation Oncology, University of Toronto, Toronto, Canada.

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380509PMC
April 2015

Phenotypic and genetic characterization of Vibrio cholerae O1 isolated from various regions of Kenya between 2007 and 2010.

Pan Afr Med J 2014 4;19. Epub 2014 Sep 4.

Centre for Disease Control (CDC), Nairobi, Kenya.

Introduction: Cholera, a disease caused by Vibrio cholerae O1 and O139 remains an important public health problem globally. In the last decade, Kenya has experienced a steady increase of cholera cases. In 2009 alone, 11,769 cases were reported to the Ministry of Public Health and Sanitation. This study sought to describe the phenotypic characteristics of the isolated V. cholerae isolates.

Methods: This was a laboratory based cross-sectional study that involved isolates from different cholera outbreaks. Seventy six Vibrio cholerae O1 strains from different geographical areas were used to represent 2007 to 2010 cholera epidemics in Kenya, and were characterized by serotyping, biotyping, polymerase chain r(PCR), pulsed-field gel electrophoresis (PFGE) and ribotyping along with antimicrobial susceptibility testing.

Results: Seventy six Vibrio cholerae O1 strains from different geographical areas were used to represent 2007 to 2010 cholera epidemics in Kenya. Serotype Inaba was dominant (88.2%) compared to Ogawa. The isolates showed varying levels of antibiotic resistance ranging from 100% susceptible to tetracycline, doxycycline, ofloxacin, azithromycin, norfloxacin and ceftriaxone to 100% resistant to furazolidone, trimethoprim-sulfamethoxazole, polymyxin-B and streptomycin. The isolates were positive for ctxA, tcpA (El Tor), rtxC genes and were biotype El Tor variant harboring classical ctxB gene. All the isolates were classified as cholera toxin (CT) genotype 1 as they had mutation in the ctxB at positions 39 and 68. All the isolates had genetically similar NotI PFGE and BglI ribotype patterns. The absence of any observed variation is consistent with a clonal origin for all of the isolates.

Conclusion: Kenya experienced cholera numerous outbreak from 2007-2010. The clinical Vibrio cholerae O1 isolates from the recent cholera epidemic were serotypes Inaba and Ogawa, Inaba being the predominant serotype. The Vibrio cholerae O1 strains were biotype El Tor variants that produce cholera toxin B (ctx B) of the classical type and were positive for ctxA, tcpA El Tor and rtxC genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11604/pamj.2014.19.8.2496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286715PMC
September 2015

Detection of avian influenza virus from fecal samples of poultry birds in Lagos State.

Afr J Med Med Sci 2014 Dec;43 Suppl:151-6

Background: Although there have been a lot of research done on Avian Influenza in the world, there are still visible indications in the Nigerian poultry farming system that the bio-security measures are not adhered to strictly. Hence, it is of great importance to identify the circulating strains of Avian Influenza virus in Nigeria, so as to prevent and control another outbreak of the disease.

Methods: Between May and June 2011, 184 stool samples were collected from seemingly healthy poultry birds in Ikorodu and Ejigbo, within Lagos state. RNA extraction using diatomaceous sand method and Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) was carried out on all samples.

Findings: Influenza virus type A 25(13.6%) was detected from poultry B (Ejigbo poultry), while there was no positive sample from poultry A (Ikorodu Poultry), the positive samples were further sub-typed, and H1 [1(4%)] was detected. Altogether, 159 (86%) of the fecal samples collected gave a. negative result for Influenza A, and also, 24(96%) out the 25 samples positive for Influenza A gave tested negative when subtyped with H1 and H3.

Interpretation: Results of the samples gotten from both poultries corroboratethe effect of poor bio-security practicesin the spread of Influenza A viruses and that some poultries in Nigeria are not adhering to proper farm bio-security practices. Also the identification of H1 subtype which is human adapted is indicative of a re- emerging potential threat to public health.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2014

Stroke prevalence amongst sickle cell disease patients in Nigeria: a multi-centre study.

Afr Health Sci 2014 Jun;14(2):446-52

Department of Haematology & Immunology, University of Nigeria Teaching hospital, Ituku-Ozalla.

Background: Stroke is a life-changing, debilitating complication of sickle cell disease (SCD). Previous studies had recorded high stroke prevalence amongst this group of patients. Nigeria has a large population of people affected by this condition and this study aims to assess the stroke prevalence in this large population.

Methodology: Stroke prevalence data from 14 physicians working in 11 tertiary health centres across the country was collated by doctors using the sickle cell registers and patient case notes. This data was then collated and used to obtain the overall stroke prevalence in adult and children.

Results: The stroke prevalence in sickle cell disease patients in Nigeria was observed to be 12.4 per 1000 patients. Prevalence in the adult patients was 17.7 per 1000 patients and 7.4 per 1000 patients in children. Twenty three percent of the affected patients had more than stroke episode.

Conclusion: The stroke prevalence in Nigeria is lower than previously recorded rates and further studies will be required to investigate other factors which may play a role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4314/ahs.v14i2.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196393PMC
June 2014

Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemia.

Nature 2014 Apr 23;508(7494):98-102. Epub 2014 Mar 23.

Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.

Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature13115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976272PMC
April 2014
-->