Safety assessment of crude aqueous methanol extract of Annona senegalensis stem bark: acute and sub-chronic toxicity studies.

Annona senegalensis Pers., (wild custard apple), is a shrub used traditionally to treat respiratory and skin diseases. Previous studies have demonstrated its anti-malaria, anti-snake envenomation and anti-cancer activities. However, its toxicological profile remains limited, particularly in male and female animals. This study aims to evaluate the safety of crude aqueous methanol extract of Annona senegalensis stem bark (AMEAS) through acute and sub-chronic toxicity studies. The stem bark of A. senegalensis was collected, air-dried, pulverized, and extracted using 70% methanol. Phytochemical screening, elemental analysis, and acute toxicity evaluation were carried out on AMEAS. Sub-chronic toxicity study was conducted on Wistar rats of both sexes at different doses administered orally for 28 days. Elemental analysis revealed the presence of heavy metals and essential mineral elements with the highest contents being calcium (59.88%) and potassium (25.39%). Acute toxicity testing showed no mortality up to 5000 mg/kg, suggesting an LD50 greater than 5000 mg/kg. In the sub-chronic toxicity study, no mortality or significant harmful effects were observed. The blood glucose decreased from 13.68 mMol/L at 250 mg/kg to 10.71 mMol/L at 1000 mg/kg, much lower than the distilled water group (17.06 mMol/L). In conclusion, the extract appeared to be well-tolerated, with no obvious adverse effects. AMEAS is rich in Calcium (Ca) and potassium (K). It has been shown to have LD50 greater than 5000 mg/kg and is assumed to be safe. On repeated use, AMEAS may cause hypoglycemia and weight loss which may be useful in managing diabetes and obesity respectively.

Case series of retinopathy of prematurity blindness in Nigeria: A wakeup call to policy makers, hospitals, ophthalmologists and paediatricians.

BACKGROUND STATEMENT: Inadequate retinopathy of prematurity (ROP) screening coverage portends a high risk for increasing the cases of ROP blindness. This study aims to report the clinical profile of pre-term babies who developed ROP blindness, highlight the usefulness in determining screening criteria and the role of private hospitals in ROP blindness prevention. CASE SERIES REPORT: Online Google form and telephone survey was conducted from May to December 2020 among paediatric ophthalmologists who provided the clinical details of ROP blind children seen between 2016 and 2020. The main outcome measured included type of the hospital of birth, gestational age, birth weight, ROP Screening and treatment, and blinding ROP Stage among children born premature. The SPSS-IBM version 26 was used for the analysis. Eighteen children blind from ROP with an equal male-to-female ratio were reported. Mean gestational age was 28.4 ± 2.2 weeks (range 26 - 34 weeks, median was 28.0 weeks). Mean birth weight was 1173.7 ± 317.9 grams (range 776 - 2100 grams, median 1125 grams). Six (33.3%) babies were born in private hospitals between 28 and 32 weeks. Sixteen (88.9%) children never had ROP screening. Fifteen (83.3%) were blind in both eyes. Six (33.3%) had Stage IVb and 12 (66.7%) Stage V. CONCLUSION: About 90% of the babies who became blind did not undergo ROP screening. It is crucial that all babies born at 34 weeks or earlier and have birth weight of < 1500 grams in public/private hospitals be screened for ROP to prevent this avoidable blindness in Nigeria.

Assessing the impact of COVID-19 on prescription patterns and antibiotic use: Insights from three military health facilities.

BACKGROUND: The COVID-19 pandemic disrupted health systems globally and there are suggestions it impacted antibiotics prescribing patterns in clinical practice. OBJECTIVES: This study aimed to assess the effects of the COVID-19 pandemic on the prescribing patterns in three Nigerian military health facilities and investigate the factors associated with antibiotic prescriptions. METHODS: This was a two-year cross-sectional retrospective study. Three hospitals and a total of 11,590 prescriptions were purposively and conveniently sampled respectively. The World Health Organisation (WHO) and International Network of Rational Use of Drugs (INRUD) prescribing indicators were used to assess for polypharmacy, injection use, use of antibiotics, use of generic drugs and prescriptions from essential drug lists for the periods of the pandemic and before the pandemic. Indicators from both periods were compared for statistical significance using the independent t-test. Generalized linear modelling was applied to assess the factors associated with antibiotic prescriptions. The relationship between the receipt of antibiotics and independent variables was presented using incident risk ratios (IRR). RESULTS: Our findings showed that all five WHO/INRUD prescribing indicators were above the reference limit for the two-year study period. The study found there was a significant statistical difference between the COVID- and non-COVID-19 periods, with polypharmacy and antibiotic use indicators elevated during the pandemic compared to the latter. COVID-19 (IRR = 1.09), comorbidity (IRR = 1.74), pregnancy (IRR = 0.93), out-of-pocket payments (IRR = 1.10) and the inpatient department (IRR = 1.51) were associated with antibiotic prescriptions. CONCLUSIONS: This provides insight on impact of the pandemic on prescription patterns and advocates for stewardship programs in clinical settings to ensure the rational use of drugs.

Gold nanoparticles spectral CT imaging and limit of detectability in a new materials contrast-detail phantom.

This study involves the synthesis, characterization, and spectral photon counting CT (SPCCT) imaging of gold nanoparticles tailored for enhancing the contrast of small cancer lesions. We used the modified Turkevich method to produce thiol-capped gold nanoparticles (AuNPs) at different concentrations (20, 15, 10, 5, 2.5, 1.25, 0.6 mg/ml). We thoroughly characterized the AuNPs using Transmission Electron Microscopy (TEM), X-ray diffraction spectroscopy (XRD), Dynamic Light Scattering (DLS), and UV-visible absorption spectroscopy. To assess the AuNPs contrast enhancing performance, we designed and built a new material contrast detail phantom for CT imaging and determined the minimum detectable concentrations of AuNPs in simulated lesions of small diameters (1, 2, 3, and 5 mm). The synthesized AuNPs are spherical with an average size of approximately 20 ± 4 nm, with maximum UV absorption occurring at 527 nm wavelength, and exhibit a face-centered cubic structure of gold according to XRD analysis. The synthesized gold nanoparticles demonstrated high contrast in SPCCT, suggesting their potential as contrast agents for imaging cancer tissues. The AuNPs image contrast was directly proportional to the AuNPs concentration. We are the first to determine that the lowest visually distinguishable contrast was achieved at a gold concentration of 5 mg/ml for a 2 mm simulated lesion. For 1 mm size lesion the smallest visible concentration was 10 mg/ml. This newly developed phantom can be used for determining the minimal concentration required for various high-Z nanoparticles to produce detectable contrast in X-ray imaging for small-size simulated lesions.

Retraction Note: Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats.

[This retracts the article DOI: 10.1007/s43188-020-00084-9.].

Ameliorative potentials of diosmin and hesperidin fractions on chlorpyriphos-induced changes in reproductive hormones, sperm characteristics, and testicular glycogen in male Wistar rats.

Reproductive deficiency is a major outcome of pesticide exposure sequel to cellular oxidative damage to sex organs. Flavonoid possess potent antioxidant capacities to mitigate pesticide related cellular injury. The present investigation examined the mitigative effect of micronized purified fractions of diosmin and hesperidin on reproductive hormones, sperm parameters, and testicular glycogen in male Wistar rats after sub-chronic Chlorpyriphos (CPF) exposure. Twenty-five male Wistar rats (120-145 g) were randomly allocated five rats per group. Group I (DW) received distilled water (2 ml/kg), Group II (S/oil) received soya oil (2 ml/kg), Group III (DAF) received Daflon at 1000 mg/kg, Group IV (CPF) received Chlorpyriphos (7.74 mg/kg), and Group V (DAF + CPF) received Daflon (1000 mg/kg) followed by CPF (7.74 mg/kg) after 30 min of Daflon. This regimen was administered daily for 60 days. After cervical venesection under light chloroform anesthesia, blood samples were examined for levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Each rat's testicular tissue was quickly cut, collected, and glycogen evaluated. Sperm concentration, motility, morphology, and viability were measured in the right caudal epididymis. Results revealed that the untreated CPF group had significantly lower FSH, LH, testosterone, testicular glycogen, and sperm concentration. Additionally, CPF group sperm characteristics were abnormal compared to other groups. These reproductive hormones, testicular glycogen, and sperm parameters improved in the Daflon-treated groups. Hence, pre-treatment with flavonoid fractions of diosmin and hesperidin mitigated CPF-induced reproductive toxicity.

ABO Blood Group Genotypes and Demographic Traits in Susceptibility to Type 1 Diabetes Mellitus in Lagos, Southwest, Nigeria.

Studies have shown that ABO blood groups and demographic traits influence susceptibility to type 1 diabetes mellitus (T1DM) and can be used in combination with insulin therapy to reduce the disease's burden. However, geographical variations exist in the influence of demographic traits and ABO blood groups on susceptibility to diseases and thus require establishing it in every locality. This study determined the influence of demographic traits and ABO blood groups on the prevalence of T1DM in Lagos, Nigeria. A structured checklist was used to collect data from the health records of non-obese 150 type 1 diabetic patients at Ayobo Primary Health Center, Lagos. The results revealed that males, with 88 participants (52.7%), constituted the majority, while females had 62 (41.3%). The age group 40 years and older had the highest proportion of participants with 37 (24.7%), followed by 31-40 years with 32 (21.30%), 21-30 years with 30 (20%), 11-20 years with 27 (18%), and 1-10 years with 24 (16%). Christianity had the highest with 74 participants (49.3%), followed by Islam with 71 participants (47.3%), and traditional religion with 5 participants (3.3%). Eight (5.3%) of the participants were primary school graduates; 34 (22.7%) were secondary school graduates; and 108 (72%) were tertiary school graduates. The Yoruba ethnic group, with 77 participants (51.3%), was the most prevalent, followed by Igbo with 50 (33.3%), and Hausa with 3 (2.0%). ABO blood group A and B (positive and negative) individuals were the most diabetic and expressed the most severe cases, while group O positive and AB negative individuals were the least diabetic. T1DM prevention should be a priority for blood group A and B residents.

Myrtenal improves memory deficits in mice exposed to radiofrequency-electromagnetic radiation during gestational and neonatal development via enhancing oxido-inflammatory, and neurotransmitter functions.

Objective: Radiofrequency-electromagnetic radiation (RF-EMR) exposure during gestational and neonatal development may interact with the foetus and neonate considered hypersensitive to RF-EMR, consequently resulting in developmental defects associated with neuropsychological and neurobehavioral disorders, including learning and memory impairment. This study assessed the potential of Myrtenal (Myrt) to improve memory deficits in C57BL/6 mice exposed to RF-EMR during gestational and neonatal development. Method: Thirty-five male mice were randomly allocated into 5 cohorts, each comprising of 7 mice. Group I was administered vehicle, Group II: RF-EMR (900 MHz); Group III: RF-EMR (900 MHz) + 100 mg/kg Myrt; Group IV: RF-EMR (900 MHz) + 200 mg/kg Myrt; and Group V: RF-EMR (900 MHz) + donepezil 0.5 mg/kg. Results: Myrt treatment improved short-term memory performance in RF-EMR (900 MHz)-exposed mice by augmenting activities of endogenous antioxidant enzymes and proinflammatory cytokines, thereby protecting the brain from oxido-inflammatory stress. Additionally, Myrt restored the homeostasis of neurotransmitters in RF-EMR-exposed animals. Conclusion: Results from the present study shows that exposure to RF-EMR impaired short-term memory in animals and altered the response of markers of oxido-inflammatory stress, and neurotransmitters. It is therefore conceivable that the recommendation of Myrt-enriched fruits may offer protective benefits for foeti and neonates prone to RF-EMR exposure.

Extraskeletal Osteosarcoma: A Case Report.

Extraskeletal osteosarcoma (ESO) is a rare form of osteosarcoma that has no attachment to bone and can be found in the thigh, retroperitoneum, chest, breast, orbit, retropharyngeal space etc. Literature about ESO is still mainly case reports and case series with few reported cases in our environment. We therefore report this 52-year-old with swelling at the left shoulder which progressed over a 3-year period. Pre-operative evaluation (both clinical, radiological and histopathological) were in favor of soft tissue sarcoma. A wide local excision showed no bony attachment intra-operatively. Histology of the specimen confirmed ESO. Patient had adjuvant chemotherapy and was followed up for 14 months before this report with no sign of local recurrence or distant metastases.

Myrtenal mitigates streptozotocin-induced spatial memory deficit via improving oxido inflammatory, cholinergic and neurotransmitter functions in mice.

The occurrence of chronic neurodegenerative disorders is on the rise, but with no effective treatment due to the paucity of information on the pathological mechanism underlying these disorders. Thus, this study investigated the role of oral administration of myrtenal in mitigating memory deficits and neuro-biochemical alterations in streptozotocin-demented mice model. Mice (n â€‹= â€‹35) were randomly allocated into five cohorts consisting of 7 mice each; Group I: Control mice received vehicle alone; Group II: streptozotocin; Group III: streptozotocin + 100 â€‹mg/kg myrtenal; Group IV: streptozotocin +200 â€‹mg/kg myrtenal; and Group V: streptozotocin â€‹+ â€‹donepezil 0.5 â€‹mg/kg. Data from this study demonstrated that the administration of streptozotocin (STZ) impaired spatial memory and induced alterations in markers of oxido-inflammatory response, cholinergic function, cytoarchitecture, and neurotransmitter levels in mice hippocampus. Notably, administration of myrtenal enhanced spatial memory performance in STZ-demented mice by improving the activities of endogenous antioxidant enzymes to protect the brain from oxido-inflammatory stress. Treatment with myrtenal also restored cholinergic function and stabilized the homeostasis of neurotransmitters in STZ-demented mice. The authors infer that fruits rich in myrtenal may be beneficial for treating patients living with dementia associated with Alzheimer's disease.

Copper-mediated construction of benzothieno[3,2-b]benzofurans by intramolecular dehydrogenative C-O coupling reaction.

An efficient method to synthesize benzothieno[3,2-b]benzofurans via intramolecular dehydrogenative C-H/O-H coupling has been developed. Good to excellent yields (64-91%) could be obtained no matter if the substituted group is electron-donating or electron-withdrawing. Notably, three-to-six fused ring thienofuran compounds could be constructed using this method. A reaction mechanism study showed that 1,1-diphenylethylene can completely inhibit the reaction. Therefore, it is a radical pathway initiated by single electron transfer between the hydroxyl of the substrate and the copper catalyst.

An experimental study on the pathophysiology of rectal prolapse.

Objectives: For decades, rectal prolapse has been hypothesized to be caused due to laxity or weakness of the pelvic floor muscles which is often sup- posed to be related to childbearing in females. However, 50% of females with rectal prolapse have been reported to be nulliparous and this hypothesis does not explain the incidence of rectal prolapse in males. The aim of this study was to evaluate the role of rectal redundancy in rectal prolapse patho- physiology. Material and Methods: Nineteen female Sprague Dawley rats (250-300 g) at 16 weeks of age were obtained from the animal center. Rats were divided into two groups as rectal mobilization (study) group (n= 9) and sham-operated control (n= 10) group. In the study group, soft dissection was applied and rectum were mobilized up from the pelvic floor to create a redundant or hypermobilized rectum.The primary outcome was the rate of rectal pro- lapse after rectal mobilization. Results: As compared to the sham-operated control group, in which none of the rats had rectal prolapse throughout the post-surgical period, rectal prolapse was observed in four of the rats in the rectal mobilization group (0% vs. 44%; p= 0.006). Being unable to increase the length of the rectums of the rats, but using only mobilization to create the redundancy, and the lack of data regarding any adhesions after surgery are the main limitations of this study. Conclusion: This study showed the role of rectal redundancy on the rectal prolapse pathophysiology.

Therapeutic drugs for SARS-CoV-2 treatment: Current state and perspective.

The disease caused by viral pneumonia called severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) declared by the World Health Organization is a global pandemic that the world has witnessed since the last Ebola epidemic, SARS and MERS viruses. Many chemical compounds with antiviral activity are currently undergoing clinical investigation in order to find treatments for SARS-CoV-2 infected patients. On-going drug-drug interaction examinations on new, existing, and repurposed antiviral drugs are yet to provide adequate safety, toxicological, and effective monitoring protocols. This review presents an overview of direct and indirect antiviral drugs, antibiotics, and immune-stimulants used in the management of SARS-CoV-2. It also seeks to outline the recent development of drugs with anti-coronavirus effects; their mono and combination therapy in managing the disease vis-à-vis their biological sources and chemistry. Co-administration of these drugs and their interactions were discussed to provide significant insight into how adequate monitoring of patients towards effective health management could be achieved.

Susceptibility of phytoplankton to the increasing presence of active pharmaceutical ingredients (APIs) in the aquatic environment: A review.

Human and veterinary pharmaceuticals either in the form of un-metabolized, incompletely metabolized, and metabolized drugs are increasingly present in aquatic ecosystems. These active pharmaceutical ingredients from pharmaceutical industries, hospitals, agricultural, and domestic discharges find their way into water systems - where they adversely affect non-target organisms like phytoplankton. Different aspects of phytoplankton life; ranging from growth, reproduction, morphology, physiology, biochemical composition, oxidative response, proteomics, and transcriptomics are altered by pharmaceuticals. This review discusses the currently available information on the susceptibility of phytoplankton to the ever-increasing presence of pharmaceutical products in the aquatic environment by focusing on the effect of APIs on the physiology, metabolome, and proteome profiles of phytoplankton. We also highlight gaps in literature concerning the salient underlining biochemical interactions between phytoplankton communities and pharmaceuticals that require an in-depth investigation. This is all in a bid to understand the imminent dangers of the contamination of water bodies with pharmaceutical products and how this process unfavorably affects aquatic food webs.

Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats.

This study aims at investigating the protective effects of flavonoid fractions of diosmin and hesperidin in mitigating sub-chronic lead acetate-induced biochemical, oxidative stress, and histopathological alterations in adult male Wistar rats. Forty animals were randomly assigned into five groups, each consisting of eight animals. Group I animals was treated with deionised water only, group II, IV, and V were administered lead acetate 90 mg/Kg body weight (1/20th of the LD50), groups III, and IV was administered Daflon (100 mg/Kg), while group V was administered Daflon (200 mg/Kg), 30 min prior treatment with lead acetate. All treatments lasted for 42 days. Blood lead levels, electrolyte parameters, zinc protoporphyrin (ZPP) levels, activities of antioxidant enzymes, and histopathology of vital organs, were evaluated following standard practice. Sub-chronic lead acetate exposure induced a decrease in levels of serum electrolytes, and activities of antioxidant enzymes, while blood lead levels, ZPP, and malondialdehyde levels were increased. Lead exposure also instigated marked variation in histopathology of vital organs. Conversely, co-treatment with graded doses of daflon improved the levels of blood lead, electrolytes, ZPP, activities of antioxidant enzymes, and histopathology of vital organs. Data obtained from the current study indicate that rats exposed to sub-chronic doses of lead acetate show increased blood lead levels, electrolyte imbalance, alongside impairment in ZPP levels, activities of antioxidant enzymes, and histopathology, while pretreatment using daflon mitigated the ensued perturbations. This, therefore, suggests that consumption of foods enriched with flavonoid fractions of diosmin and hesperidin may be beneficial for individuals inhabiting lead-polluted environments.

Breast Cancer Screening Practices in a Tertiary Care Center in the State of Qatar: A Cross-Sectional Survey.

INTRODUCTION: Breast cancer is the most common cancer in females. In Qatar, mortality related to breast cancer came in third after lung cancer and leukemia. In this study, we aim to comprehensively evaluate the rate of internal medicine residents and faculty compliance with breast cancer screening in Hamad Medical Corporation (Doha, Qatar), as well as to identify barriers and facilitators that could potentially augment changes to enhance physician-led cancer screening. METHODS: A cross-sectional web-based survey was distributed among internal medicine physicians between December 2018 and March 2019 at a tertiary medical centre. It focused on the knowledge, attitude, and practice of physicians regarding breast cancer screening guidelines and explored potential barriers and proposed solutions. Chi-square and t-test statistics were used to draw conclusions where appropriate. RESULTS: A total of 158 physicians responded to the survey, with a response rate of 61%. 75.9% were postgraduate trainees. Around three-quarters of the physicians mentioned that they would recommend breast cancer screening for their age-appropriate average-risk patients. There was a statistically significant difference between the trainees, consultants, and specialists regarding the modality of choice, where the majority of the trainees opted mammogram every 2 or 3 years while 44.4% of the consultants indicated yearly self-breast exam (p<0.001). The percentage of survey participants who rarely to never offer breast cancer screening in the outpatient settings was 37.8%. Unclear pathway (40%) and lack of time in clinic/ward rounds (26.5%) were the major reported barriers for cancer screening. CONCLUSION: In the current era of personalized medicine, physicians should be more oriented to local guidelines to provide optimal care to their patients. While the attitude towards breast cancer screening is positive, the overall compliance with the national recommendations is sub-optimal. Further initiatives and intervention programs are required to promote the breast cancer screening in Qatar.

Comparative effectiveness and safety of direct-acting oral anticoagulants (DOACS) for the reduction of recurrent venous thromboembolism in cancer patients: A protocol for systematic review and network meta-analysis using a generalized pairwise modeling methodology.

BACKGROUND: There has been a significant improvement in both our understanding and therapeutic choices available to clinicians for the management of cancer associated thrombosis (CAT). Even with the recent publication of a systematic review and landmark trials demonstrating the non-inferiority of DOACS-based anticoagulation strategy compared to the standard of care in patients with CAT, there is unresolved uncertainty regarding the exact hierarchy of risks and effectiveness of various DOAC analogues in these cohorts of patients. METHOD: We will carry out a network meta-analyses, utilizing a novel generalized pairwise methodology to generate direct and indirect comparisons between the various DOAC analogues. We will search the following databases for studies that satisfies pre-specified inclusions criteria; these include PubMed, EMBASE, Cochrane library, Clinicaltrials.gov, conference abstracts among other sources. The primary efficacy and safety outcomes are recurrent VTE and major hemorrhagic events, respectively. Two reviewers will Search the databases independently with the view to identify studies that meet eligibility criteria. The methodological quality of the included studies will be determined using a recently validated risk of bias assessment tool. RESULTS: We expect that the result of this review will ascertain the hierarchy of risks and effectiveness of various DOAC analogues in patients with CAT. CONCLUSION: Results of this review will assist in informed decisions making regarding therapeutic guidelines of DOAC in CAT.

Fungal Malignant Otitis Externa Involves a Cascade of Complications Culminating in Pseudoaneurysm of Internal Maxillary Artery: A Case Report.

BACKGROUND Pseudomonal infection is the most common cause of malignant otitis externa (MOE), which typically affects elderly diabetic patients. Fungi are a rare cause of MOE. MOE can be life-threatening if not recognized and treated promptly. It can result in a wide spectrum of complications, including skull-base osteomyelitis, cranial nerve palsy, cerebral venous thrombosis, and brain abscess. Pseudoaneurysm formation of the intracranial vessels is a life-threatening complication of MOE that is seldom reported in the literature. CASE REPORT We report the case of a 66-year-old diabetic man with MOE who was initially treated with antipseudomonal antibiotics after negative initial culture results. His MOE resulted in a cascade of complications, including facial nerve palsy, skull base osteomyelitis, and sigmoid sinus thrombosis, and culminated in left maxillary artery pseudoaneurysm formation resulting in massive epistaxis and hemodynamic instability. Endovascular embolization resulted in a successful obliteration of the pseudoaneurysm. A subsequent functional endoscopic sinus surgical (FESS) tissue biopsy confirmed Candida glabrata as the etiological agent. The patient was successfully treated with antibiotics and antifungal and anticoagulation therapy, and was discharged home in good condition. CONCLUSIONS A high index of suspicion for the diagnosis of fungal MOE, particularly in intractable cases of MOE with negative initial cultures, should be maintained. Pseudoaneurysm formation is a life-threatening complication of MOE that is seldom reported in the literature and should be suspected in any patient with MOE who presents with epistaxis or intracranial bleeding.

Differential bioavailability of copper complexes to bioluminescent Pseudomonas fluorescens reporter strains.

Increased levels of Cu in agricultural soils are of concern, because Cu toxicity may adversely affect important soil microorganisms, including pseudomonads. Because total metal concentrations correlate poorly with bioavailability and toxicity, a need exists for more information linking Cu speciation, bioavailability, and toxicity. The objective of the present study was to determine the bioavailability of different Cu complexes to Pseudomonas spp. A Cu-specific bioluminescent Pseudomonas fluorescens reporter strain was used to determine bioavailable Cu, which was operationally defined as those Cu species that induced expression of bioluminescence. Another strain of P. fluorescens, which continuously expressed bioluminescence, was used as a toxicity reporter. Experiments were performed in a defined aqueous medium containing 0.04 microM Cu, which was amended with ethylenediaminetetraacetic acid (EDTA), citrate, or a well-characterized pool of dissolved organic matter (DOM). Bioluminescence emitted by the biosensors was related to data for Cu speciation obtained by geochemical modeling. Changes in Cu bioavailability in the presence of EDTA coincided with modeled changes in Cu2+ activity, indicating that Cu-EDTA complexes were not bioavailable to the Cu-specific reporter. In contrast, changes of Cu bioavailability in the presence of citrate did not correspond to changes in Cu2+, indicating that Cu-citrate complexes were fully bioavailable to the reporter strain. Finally, the response of the Cu-reporter strain to Cu in the presence of DOM indicated that Cu formed bioavailable as well as unavailable complexes with DOM. We conclude that free Cu2+ activity is a poor predictor of Cu bioavailability to Pseudomonas spp. in samples containing organic ligands.

Progress towards elimination of measles in Kenya, 2003-2016.

INTRODUCTION: Measles is targeted for elimination in the World Health Organization African Region by the year 2020. In 2011, Kenya was off track in attaining the 2012 pre-elimination goal. We describe the epidemiology of measles in Kenya and assess progress made towards elimination. METHODS: We reviewed national case-based measles surveillance and immunization data from January 2003 to December 2016. A case was confirmed if serum was positive for anti-measles IgM antibody, was epidemiologically linked to a laboratory-confirmed case or clinically compatible. Data on case-patient demographics, vaccination status, and clinical outcome and measles containing vaccine (MCV) coverage were analyzed. We calculated measles surveillance indicators and incidence, using population estimates for the respective years. RESULTS: The coverage of first dose MCV (MCV1) increased from 65% to 86% from 2003-2012, then declined to 75% in 2016. Coverage of second dose MCV (MCV2) remained < 50% since introduction in 2013. During 2003-2016, there were 26,188 suspected measles cases were reported, with 9043(35%) confirmed cases, and 165 deaths (case fatality rate, 1.8%). The non-measles febrile rash illness rate was consistently > 2/100,000 population, and "80% of the sub-national level investigated a case in 11 of the 14 years. National incidence ranged from 4 to 62/million in 2003-2006 and decreased to 3/million in 2016. The age specific incidence ranged from 1 to 364/million population and was highest among children aged < 1 year. CONCLUSION: Kenya has made progress towards measles elimination. However, this progress remains at risk and the recent declines in MCV1 coverage and the low uptake in MCV2 could reverse these gains.