Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-13C]pyruvate in vivo.

Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe a first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. Biocompatible formulations of hyperpolarized [1-13C]pyruvate in, both, methanol-water mixtures, and ethanol-water mixtures followed by dilution with saline and catalyst filtration were prepared and injected into healthy Sprague Dawley and Wistar rats. Effective hyperpolarization-catalyst removal was performed with silica filters without major losses in hyperpolarization. Metabolic conversion of pyruvate to lactate, alanine, and bicarbonate was detected in vivo. Pyruvate-hydrate was also observed as minor byproduct. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop safe, and scalable molecular imaging.

Addressing Unmet Surgical Needs in an Underserved Nigerian Community: Report of a 'Town and Gown' Initiative.

BACKGROUND: Access to quality and timely care prevents unnecessary deaths and morbidity from potentially curable surgical diseases. This study describes the magnitude of unmet surgical needs in a Nigerian community and describes the experiences garnered during a surgical outreach organized by a tertiary institution in an underserved community. METHODS: This is a descriptive study highlighting details of a surgical outreach to a community in south-Western part of Nigeria. The project was based on a collaboration between a University Teaching Hospital (gown) and the community (town). Details of the patients' demographic and disease characteristics as well as barriers to seeking medical care were obtained. The operational workflow, treatment offered, and outcomes are highlighted. Results are presented as descriptive statistics. RESULTS: Over a two-day period, 83 out of 3,056 patients who were screened had surgically treatable conditions (2.7%), predominantly hernias (37, 46.6%), goitres (13, 15.7%) and soft tissue swellings (9, 10.8%). The majority were adults (56, 67.5%) while 27 (32.5%) were in the paediatric age group. The mean duration of symptoms was 8.64 months ± 9.5 months. About half of the patients (46.9%) had never visited a medical facility on account of their index illnesses. Lack of funds was cited by many patients as the main reason for having not presented at a hospital. Sixty-three surgical operations were performed with no peri-operative adverse events. CONCLUSION: Lack of financial access was the major barrier to surgical care in the sampled community. Moving from 'gown to town' helped address a significant proportion of the unmet needs over a relatively short period. Tertiary hospitals can provide surgical oversight to communities within their jurisdiction using this approach.

CONTEXTE: L'accès à des soins de qualité et en temps opportun permet d'éiter les décès et la morbidité inutiles dus à des maladies chirurgicales potentiellement curables. Cette étude décrit l'ampleur des besoins chirurgicaux non satisfaits dans une communauté nigériane et décrit les expériences recueillies au cours d'une action chirurgicale organisée par une institution tertiaire dans une communauté mal desservie. MÉTHODES: Il s'agit d'une étude descriptive mettant en évidence les détails d'une action chirurgicale dans une communauté du sud-ouest du Nigeria. Le projet était basé sur une collaboration entre un hôpital universitaire (ville) et la communauté (ville). Les détails des caractéristiques démographiques et pathologiques des patients ainsi que les obstacles à la recherche de soins médicaux ont été obtenus. Le déroulement des opérations, le traitement proposé et les résultats sont mis en évidence. Les résultats sont présentés sous forme de statistiques descriptives. RÉSULTATS: Sur une période de deux jours, 83 des 3056 patients examinés présentaient des affections pouvant être traitées chirurgicalement (2,7 %), principalement des hernies (37, 46,6 %), des goitres (13, 15,7 %) et des tuméfactions des tissus mous (9, 10,8 %). La majorité des patients étaient des adultes (56, 67,5 %), tandis que 27 (32,5 %) appartenaient au groupe d'âge pédiatrique. La durée moyenne des symptômes était de 8,64 mois ±9,5 mois. Environ la moitié des patients (46,9 %) ne s'étaient jamais rendus dans un établissement médical en raison de leurs maladies index. Le manque de moyens financiers a été cité par de nombreux patients comme la principale raison pour laquelle ils ne s'étaient pas présentés à l'hôpital. Soixante-trois opérations chirurgicales ont été réalisées sans aucun événement indésirable périopératoire. CONCLUSION: Le manque d'accès financier était le principal obstacle aux soins chirurgicaux dans la communauté échantillonnée. Le passage de la ville à l'hôpital a permis de répondre à une proportion importante des besoins non satisfaits sur une période relativement courte. Les hôpitaux tertiaires peuvent fournir une supervision chirurgicale aux communautés de leur juridiction en utilisant cette approche. Mots clés: Chirurgie, Besoins non satisfaits, Nigeria, Communauté mal desservie.

From the Breast to the Finger - A Case Report of Acrometastasis.

BACKGROUND: Acrometastasis is an unusual presentation that is associated with a poor prognosis. SUMMARY OF CASE: We report a case of an advanced breast cancer in a Nigerian woman, with clinical, radiological and histopathological features of lung, brain, and distal phalanx metastases. We report this case to highlight the need to have a high index of suspicion for acrometastasis as well as to emphasize the effect and challenges of managing metastatic breast cancer in a low-income country. CONCLUSION: Breast cancer metastasis to the bones of the hand is a rare condition and associated with poor prognosis.

CONTEXTE: L'acrométastase est une présentation inhabituelle associée à un pronostic défavorable. RÉSUMÉ DU CAS: Nous rapportons le cas d'un cancer du sein avancé chez une femme nigériane, présentant des caractéristiques cliniques, radiologiques et histopathologiques de métastases pulmonaires, cérébrales et de la phalange distale. Nous rapportons ce cas pour souligner la nécessité d'avoir un haut degré de suspicion pour l'acrométastase ainsi que pour souligner les effets et les défis de la prise en charge du cancer du sein métastatique dans un pays à faible revenu. CONCLUSION: La métastase du cancer du sein aux os de la main est une condition rare et associée à un pronostic défavorable. MOTS-CLÉS: Cancer du sein, Métastase, Acrométastase.

Antimicrobial resistance pattern of methicillin-resistant Staphylococcus aureus isolated from sheep and humans in Veterinary Hospital Maiduguri, Nigeria.

Background and Aim: Methicillin-resistant Staphylococcus aureus (MRSA), an important opportunistic pathogen, is a Gram-positive coccus known to be resistant to ß-lactam antibiotics. Its virulence depends on a large range of factors, mainly extracellular proteins, such as enzymes and exotoxins, that contribute to causing a wide range of diseases in human and animal species. The major reasons for the success of this pathogen are its great variability, which enables it to occur and thrive at different periods and places with diverse clonal types and antibiotic resistance patterns within regions and countries. Infections caused by antibiotic-resistant S. aureus bring about serious problems in the general population (humans and animals). Infections with these pathogens can be devastating, particularly for the very young, adults and immunocompromised patients in both humans and animals. This study aimed to determine the presence of MRSA in both apparently healthy and sick sheep brought to the veterinary hospital as well as veterinary staff and students on clinical attachment in the hospital. Materials and Methods: A total of 200 nasal swab samples were collected aseptically from sheep and humans (100 each) for the isolation of MRSA. The samples were processed by appropriately transporting them to the laboratory, then propagated in nutrient broth at 37°C for 24 h followed by subculturing on mannitol salt agar at 37°C for 24 h, to identify S. aureus. This was followed by biochemical tests (catalase and coagulase tests) and Gram staining. MRSA was isolated using Clinical Laboratory Standard Institute (CLSI) guideline and confirmed by plating onto Oxacillin (OX) Resistance Screening Agar Base agar. The antimicrobial susceptibility pattern of the MRSA isolates was determined using the disk diffusion method against 12 commonly used antimicrobial agents. Results: The total rate of nasal carriage of S. aureus and MRSA was found to be 51% and 43% in sheep and humans, respectively. The MRSA prevalence in male and female sheep was 18% and 8%, while 9% and 8% were for male and female human samples, respectively. The antimicrobial susceptibility test showed 100% resistance to OX, cefoxitin, oxytetracycline, cephazolin, and penicillin-G (Pen) by MRSA isolates from humans. Conversely, there was 100% susceptibility to ciprofloxacin, imipenem, and gentamicin; for linezolid (LZD), it was 87.5%, norfloxacin (NOR) (71%), and erythromycin (ERY) (50%) susceptibility was recorded. The MRSA isolates from sheep recorded 100% resistance to the same set of drugs used for human MRSA isolates and were equally 100% susceptible to gentamicin, imipenem, LZD, ciprofloxacin, NOR (92%), and ERY (50%). Conclusion: This study determined the presence of MRSA in sheep and humans from the Veterinary Hospital, Maiduguri. It appears that certain drugs such as ciprofloxacin, imipenem, and gentamicin will continue to remain effective against MRSA associated with humans and sheep. Reasons for the observed patterns of resistance must be explored to reduce the burdens of MRSA resistance. Furthermore, the present study did not confirm the MRSA resistance genes such as mecA and spa typing to ascertain the polymorphism in the X-region using appropriate molecular techniques. Hence more studies need to be conducted to elucidate these findings using robust techniques.

Identification of potent inhibitors of ATP synthase subunit c (AtpE) from Mycobacterium tuberculosis using in silico approach.

ATP synthase subunit c (AtpE) is an enzyme that catalyzes the production of ATP from ADP in the presence of sodium or proton gradient from Mycobacterium tuberculosis (MTB). This enzyme considered an essential target for drug design and shares the same pathway with the target of Isoniazid. Thus, this enzyme would serve as an alternative target of the Isoniazid. The three dimensional (3D) model structure of the AtpE was constructed based on the principle of homology modeling using the Modeller9.16. The developed model was subjected to energy minimization and refinement using molecular dynamic (MD) simulation. The minimized model structure was searched against Zinc and PubChem database to determine ligands that bind to the enzyme with minimum binding energy using RASPD and PyRx tool. A total of 4776 compounds capable of bindings to AtpE with minimum binding energy were selected. These compounds further screened for physicochemical properties (Lipinski rule of five). All the compounds that possessed the desirable property selected and used for molecular docking analysis. Five (5) compounds with minimum binding energies ranged between ─8.69, and ─8.44 kcal/mol, less than the free binding energy of ATP were selected. These compounds further screened for the absorption, distribution, metabolism, excretion, and toxicity (ADME and toxicity) properties. Of the five compounds, three (ZINC14732869, ZINC14742188, and ZINC12205447) fitted all the ADME and toxicity properties and subjected to MD simulation and Molecular Mechanics Generalized Born and Surface Area (MM-GBSA) analyses. The results indicated that the ligands formed relatively stable complexes and had free binding energies, less than the binding energy of the ATP. Therefore, these ligands considered as prospective inhibitors of MTB after successful experimental validation.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

Off-line commissioning of EBIS and plans for its integration into ATLAS and CARIBU.

An Electron Beam Ion Source Charge Breeder (EBIS-CB) has been developed at Argonne to breed radioactive beams from the CAlifornium Rare Isotope Breeder Upgrade (CARIBU) facility at Argonne Tandem Linac Accelerator System (ATLAS). The EBIS-CB will replace the existing ECR charge breeder to increase the intensity and significantly improve the purity of reaccelerated radioactive ion beams. The CARIBU EBIS-CB has been successfully commissioned offline with an external singly charged cesium ion source. The performance of the EBIS fully meets the specifications to breed rare isotope beams delivered from CARIBU. The EBIS is being relocated and integrated into ATLAS and CARIBU. A long electrostatic beam transport system including two 180° bends in the vertical plane has been designed. The commissioning of the EBIS and the beam transport system in their permanent location will start at the end of this year.

Effects of fasting on intraocular pressure in a black population.

INTRODUCTION: There is a dearth of literature available on the effects of fasting on Intraocular pressure (IOP) among all races and worldwide. OBJECTIVES: To determine the effects of fasting on IOP in a black African population. MATERIALS AND METHODS: A population-based survey utilizing multistage random sampling techniques was carried out among healthy adult Muslims who were examined before and during Ramadan fast in Osogbo, Nigeria. Demographics were obtained, visual acuities, clinical examination of both eyes, and IOPs were done. Weights and waist circumference were measured. Data were analyzed using Statistical Package for Social Sciences ( SPSS) Version 16. Analysis generated frequencies and cross tabulations, whereas statistical significant values were derived using paired sample t-test and P < 0.05. RESULTS: A total of 60 subjects with 120 eyes were examined. Mean age was 42.3 years standard deviation (SD) 16.7, and the male to female ratio was 3:2. Majority were professionals (33.3%). Only 18.3% had less than secondary school education. Over 90% had normal vision (6/5-6/18). Before and during fasting, the mean weights were 65.92 kg SD 12.98 and 65.29 kg SD 12.41 with a reduction of 0.63 kg SD 3.82 (P = 0.214, 95% confidence interval (CI): 0.372-1.626); and the mean waist circumference was 87.20 cm SD 12.39 and 81.78 cm SD 11.65 (P = 0.000, 95% CI 4.128-6.720), respectively. Mean IOPs were 15.98 mmHg SD 3.11 and 14.08 mmHg SD 2.71 before and during fasting, respectively (P = 0.000, 95% CI 0.98558-2.82798). CONCLUSIONS: The study shows that fasting significantly reduced IOP in an ocularly healthy black African population.

Honeybee sting of the sclera: occular features, treatment, outcome and presumed pathogenesis.

Ocular bee sting injury has caused several reactions in the eye but has rarely been reported among local African farmers, and Nigerians in particular. This case seeks to report the first ocular and external eye reactions following a honey bee sting of the eye through the sclera, highlighting the treatment and outcome. Oral interview, clinical examination and external photographs were used to obtain and document findings. Medical treatment was instituted as soon as subject presented. There was complete inflammatory resolution within a week, normal vision and no evidence of stinger migration after four weeks of follow up. The wound site healed with ciliary staphyloma. The role of physical properties, immunological and genetics interplay and the presumed pathogenesis is further discussed. Health education on early presentation and avoidance of harmful traditional eye medications should be promoted among the farming populations in our communities, in order to prevent blinding complications.

Awareness of and Attitude towards glaucoma among an adult rural population of Osun State, Southwest Nigeria.

PURPOSE: To obtain baseline data and assess the level of awareness and attitudes towards glaucoma among rural communities of Osun State, Nigeria. MATERIALS AND METHODS: This was a community-based study that involved interviews and descriptive cross-sectional analysis. Serial-recruitment was performed of consenting participants who presented at a community-based screening service in March 2011. Socio-demographic data and information about glaucoma were obtained through face-to-face semi-structured questionnaires. RESULTS: The study population comprised 259 respondents (mean age 49.73 ± 16.6 years; range 18 to 90 years). There were 159 females (61.4%). Skilled workers were the most common 130/259 (50.3%) participants. Only 41 (15.8%; 95% CI: 11.4-20.2) participants had ever heard of glaucoma. Sources of information were from visits to an eye clinic for 21/41 (51.2%; 95% CI: 35.9-66.5) participants and 15/41 (36.6%) participants who know someone with glaucoma. Reponses to the causes of glaucoma included 20/41 (48.8%; 33.5-64.1) participant who said 'I don't know' and 24.4% of participants who responded 'curse-from-God'. Responses to questions on treatment included 20/41 (48.8%) participants who responded 'I don't know how it can be treated' and 10/41 (36.6%) said 'medically'. Thirty 30/41 (73.2%) participants would refuse surgery, half of them because 'it cannot cure or reverse the disease' while (26.7%) would refuse out of 'fear'. Only 8/41 (19.5%; 95% CI: 7.4-31.6) would accept surgery for maintenance. Statistically significant predictors of glaucoma awareness were older participants, males and skilled workers (teachers) (P = 0.028, P = 0.018, P = 0.0001, respectively). CONCLUSIONS: The outcomes of study indicate a low level of awareness of glaucoma. Health education at all levels of health and eye care services is required to prevent ocular morbidity and irreversible blindness from glaucoma.

Prevalence of asthma and respiratory symptoms in children in a low socio-economic status area of Nigeria.

SETTING: Warri and environs in the Niger Delta, in the Southern region of Nigeria. OBJECTIVE: To investigate the burden of respiratory illness in children in the Niger Delta. DESIGN: A cross-sectional survey of 1397 schoolchildren aged 7-14 years in areas of low socio-economic status (SES), using written questionnaires in English based on the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, with explanation of symptoms. RESULTS: The prevalence of doctor-diagnosed asthma was 0.9% (95%CI 0.4-1.3), and wheeze in the last 12 months was 5.4% (95%CI 4.3-6.6). The prevalence of other respiratory symptoms was high, in particular night cough 23.3% (95%CI 21.1-25.5), rhinitis 19.2% (95%CI 17.1-21.3) and phlegm production 16.6% (95%CI 14.7-18.6). Risk of wheeze in the younger age groups was twice (OR 2.09, 95%CI 1.29-3.39) that of older ages after controlling for sex and geographical area. Risk of asthma in urban children was reduced (OR 0.15, 95%CI 0.05-0.50) compared to rural children after controlling for age and sex. Urban children also had a lower risk of rhinitis, exercise limitations and absenteeism due to respiratory illness than rural children. CONCLUSION: The prevalence of symptoms of allergic disease was lower than in the African centres in the ISAAC surveys conducted in urban centres. Doctor-diagnosed asthma is likely to be a poor indicator of asthma in low SES areas of developing countries due to health care access issues.

Design of the injection beamline for the Californium Rare Isotope Breeder Upgrade electron beam ion source charge breeder.

The design of the ion injection line connecting the electron beam ion source (EBIS) charge breeder and the Californium Rare Isotope Breeder Upgrade radio frequency quadrupole cooler-buncher at the Argonne Tandem Linear Accelerator System was investigated with particle tracking simulations. The injection line was configured to accommodate several differential pumping sections, individual optical components were optimized to minimize emittance growth, and the ion beam parameters were matched with the EBIS electron beam acceptance to minimize losses upon injection.

Traffic air pollution and other risk factors for respiratory illness in schoolchildren in the niger-delta region of Nigeria.

BACKGROUND: Association of childhood respiratory illness with traffic air pollution has been investigated largely in developed but not in developing countries, where pollution levels are often very high. OBJECTIVES: In this study we investigated associations between respiratory health and outdoor and indoor air pollution in schoolchildren 7-14 years of age in low socioeconomic status areas in the Niger Delta. METHODS: A cross-sectional survey was carried out among 1,397 schoolchildren. Exposure to home outdoor and indoor air pollution was assessed by self-report questionnaire. School air pollution exposures were assessed using traffic counts, distance of schools to major streets, and particulate matter and carbon monoxide measurements, combined using principal components analysis. Hierarchical logistic regression was used to examine associations with reported respiratory health, adjusting for potential confounders. RESULTS: Traffic disturbance at home (i.e., traffic noise and/or fumes evident inside the home vs. none) was associated with wheeze [odds ratio (OR) = 2.16; 95% confidence interval (CI), 1.28-3.64], night cough (OR = 1.37; 95% CI, 1.03-1.82), phlegm (OR = 1.49; 95% CI, 1.09-2.04), and nose symptoms (OR = 1.40; 95% CI, 1.03-1.90), whereas school exposure to a component variable indicating exposure to fine particles was associated with increased phlegm (OR = 1.38; 95% CI, 1.09-1.75). Nonsignificant positive associations were found between cooking with wood/coal (OR = 2.99; 95% CI, 0.88-10.18) or kerosene (OR = 2.83; 95% CI, 0.85-9.44) and phlegm compared with cooking with gas. CONCLUSION: Traffic pollution is associated with respiratory symptoms in schoolchildren in a deprived area of western Africa. Associations may have been underestimated because of nondifferential misclassification resulting from limitations in exposure measurement.

Metal detectors: security vs. customer service.

The pros and cons of metal detectors in hospitals should be reviewed again, the author recommends, in light of new conditions that are making emergency departments even more violent and volatile. In this article, he reports on the results of three years employment of metal detection.

The genetic aetiology of late-onset chronic progressive cerebellar ataxia. A population-based study.

BACKGROUND: An increasing number of dominant and recessive disorders have been associated with late onset chronic progressive ataxia (LOCA) complicating the formulation of a rational diagnostic strategy. Furthermore, there is marked geographic and ethnic variation in the relative importance of these individual disorders and the cause of such observed variation remains unexplained. METHODS: We have systematically investigated a population-based cohort of patients with chronic progressive LOCA for SCA 1, 2, 3, 6, 7, 8, 10, 12, 17, FXTAS and FRDA. In addition we have examined repeat length polymorphism in chromosomes from a genetically homogeneous and representative control population to investigate the association of high-normal repeats and disease prevalence. RESULTS: A total of 178 patients including 55 familial cases segregating in 38 kindreds and 123 sporadic were investigated. Pathological expansions were identified in 11/38 (28.9 %) of families and in 5/123 (4.1 %) of sporadic patients. The most frequent diagnoses were SCA6 (6 families and 1 sporadic patient), DRPLA (4 families) and SCA8 (1 family). In addition, one elderly female patient was identified with "possible FXTAS". Six (2 %) control patients were noted to have expanded SCA8 alleles. CONCLUSIONS: SCA6 and DRPLA were the most frequent genetic diagnoses identified. Patterns of high-normal allele frequency in this UK population were distinct compared to other ethnic groups but this was poorly predictive of the distribution of disease in this region. The relative contribution of new mutation formation and founder effects to the prevalence of familial ataxia is uncertain, and further exploration of these factors will require detailed analysis of disease allele haplotypes and meiotic instability of intermediate length alleles.

Cross sections of spallation residues produced in 1A GeV 208Pb on proton reactions.

Spallation residues produced in 1 GeV per nucleon 208Pb on proton reactions have been studied using the Fragment Separator facility at GSI. Isotopic production cross sections of elements from 61Pm to 82Pb have been measured down to 0.1 mb with a high accuracy. The recoil kinetic energies of the produced fragments were also determined. The obtained cross sections agree with most of the few existing gamma-spectroscopic data. The data are compared with different intranuclear-cascade and evaporation-fission models. Drastic deviations were found for a standard code used in technical applications.

Arthroscopic resection of dorsal wrist ganglia and treatment of recurrences.

From 1995 to 1998, 30 patients with dorsal wrist ganglia and four with recurrent dorsal ganglia underwent arthroscopic resection. At a mean follow-up of 16 months, no complications were seen, but minimal pain persisted in three patients. Two recurrences were seen after arthroscopic resection of primary ganglia.

[MRI in the postoperative assessment of pseudoarthrosis of the scaphoid bone treated by corticocancellous bone graft. Report of 31 cases]. / L'IRM dans le contrôle des pseudarthroses du scaphoïde carpien traitées par greffe cortico-spongieuse. A propos de 31 cas étudiés.

Thirty one scaphoid pseudarthroses treated by corticocancellous bone graft between November 1985 and December 1988 were reviewed with a mean follow-up of 33.9 months. Clinical examination assessed pain, wrist mobility, and strength of grip. Radiological assessment evaluated consolidation of the corticocancellous graft, the presence or absence of graft resorption and the possible presence of radiocarpal osteoarthritis. A discordance between clinical and radiographic results was observed. Six patients had an excellent or good clinical result, but a poor radiological result and one patient with a poor clinical result presented an excellent radiological result. We therefore decided to use MRI to more clearly define the cause of this discordance and to verify the viability of the graft.