Lymphatic Filariasis Control in Tanzania: Effect of Six Rounds of Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission.

Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.\ud The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination

Pulmonary apelin levels and effects in rats with hypoxic pulmonary hypertension

SummaryBackgroundThe peptide apelin is localised in the vascular endothelium and highly expressed in pulmonary tissue. The aim of this study was to investigate whether apelin could be a potential lung-derived plasma marker for pulmonary hypertension, and study the effect of apelin in pulmonary arteries.MethodsApelin protein levels were measured in the lung, right ventricle, and plasma from normoxic and chronic hypoxic rats with pulmonary hypertension. Isolated intrapulmonary arteries were mounted in microvascular myographs and the effect of apelin investigated. Finally, the distribution of apelin receptors in pulmonary tissue was visualised by immunohistochemistry.ResultsTotal pulmonary apelin content was not changed by hypoxia. Right ventricular apelin concentrations and content were lower than in the lung, but increased substantially in hypoxia in correlation with right ventricular pressure. Plasma apelin did not reflect pulmonary or right ventricular apelin levels. In pulmonary arteries from normoxic rats, apelin inhibited vasoconstriction to endothelin-1 and angiotensin-II. However, in arteries from hypoxic rats, apelin failed to inhibit contraction to angiotensin-II and endothelin-1. No difference in immunoreaction for apelin receptors was found in lung sections and arteries from normoxic versus chronic hypoxic rats.ConclusionsApelin changes in the right ventricle seem more specific for pulmonary hypertension than do changes in pulmonary tissue, which does not speak in favour of apelin as a lung-derived marker for this disease. During normoxic conditions, apelin has a modulating effect on vasoconstriction which is lost in chronic hypoxia. This may reflect alterations in the signal transduction downstream of the apelin receptor

Wnt3a nanodisks promote ex vivo expansion of hematopoietic stem and progenitor cells

BACKGROUND: Wnt proteins modulate development, stem cell fate and cancer through interactions with cell surface receptors. Wnts are cysteine-rich, glycosylated, lipid modified, two domain proteins that are prone to aggregation. The culprit responsible for this behavior is a covalently bound palmitoleoyl moiety in the N-terminal domain. RESULTS: By combining murine Wnt3a with phospholipid and apolipoprotein A-I, ternary complexes termed nanodisks (ND) were generated. ND-associated Wnt3a is soluble in the absence of detergent micelles and gel filtration chromatography revealed that Wnt3a co-elutes with ND. In signaling assays, Wnt3a ND induced β-catenin stabilization in mouse fibroblasts as well as hematopoietic stem and progenitor cells (HSPC). Prolonged exposure of HSPC to Wnt3a ND stimulated proliferation and expansion of Lin(−) Sca-1(+) c-Kit(+) cells. Surprisingly, ND lacking Wnt3a contributed to Lin(−) Sca-1(+) c-Kit(+) cell expansion, an effect that was not mediated through β-catenin. CONCLUSIONS: The data indicate Wnt3a ND constitute a water-soluble transport vehicle capable of promoting ex vivo expansion of HSPC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12951-016-0218-5) contains supplementary material, which is available to authorized users

Level Crossing Analysis of the Stock Markets

We investigate the average frequency of positive slope $\nu_{\alpha}^{+}$, crossing for the returns of market prices. The method is based on stochastic processes which no scaling feature is explicitly required. Using this method we define new quantity to quantify stage of development and activity of stocks exchange. We compare the Tehran and western stock markets and show that some stocks such as Tehran (TEPIX) and New Zealand (NZX) stocks exchange are emerge, and also TEPIX is a non-active market and financially motivated to absorb capital.Comment: 6 pages and 4 figure

The transition from the adiabatic to the sudden limit in core level photoemission: A model study of a localized system

We consider core electron photoemission in a localized system, where there is a charge transfer excitation. The system is modelled by three electron levels, one core level and two outer levels. The model has a Coulomb interaction between these levels and the continuum states into which the core electron is emitted. The model is simple enough to allow an exact numerical solution, and with a separable potential an analytic solution. We calculate the ratio r(omega) between the weights of the satellite and the main peak as a function of the photon energy omega. The transition from the adiabatic to the sudden limit takes place for quite small photoelectron kinetic energies. For such small energies, the variation of the dipole matrix element is substantial and described by the energy scale Ed. Without the coupling to the photoelectron, the corresponding ratio r0(omega) is determined by Ed and the satellite excitation energy dE. When the interaction potential with the continuum states is introduced, a new energy scale Es=1/(2Rs^2) enters, where Rs is a length scale of the interaction potential. At threshold there is typically a (weak) constructive interference between intrinsic and extrinsic contributions, and the ratio r(omega)/r0(omega) is larger than its limiting value for large omega. The interference becomes small or weakly destructive for photoelectron energies of the order Es. For larger energies r(omega)/r0(omega) therefore typically has a weak undershoot. If this undershoot is neglected, r(omega)/r0(omega) reaches its limiting value on the energy scale Es.Comment: 18 pages, latex2e, 13 eps figure

Identification of a novel biomarker candidate, a 4.8-kDa peptide fragment from a neurosecretory protein VGF precursor, by proteomic analysis of cerebrospinal fluid from children with acute encephalopathy using SELDI-TOF-MS

<p>Abstract</p> <p>Background</p> <p>Acute encephalopathy includes rapid deterioration and has a poor prognosis. Early intervention is essential to prevent progression of the disease and subsequent neurologic complications. However, in the acute period, true encephalopathy cannot easily be differentiated from febrile seizures, especially febrile seizures of the complex type. Thus, an early diagnostic marker has been sought in order to enable early intervention. The purpose of this study was to identify a novel marker candidate protein differentially expressed in the cerebrospinal fluid (CSF) of children with encephalopathy using proteomic analysis.</p> <p>Methods</p> <p>For detection of biomarkers, CSF samples were obtained from 13 children with acute encephalopathy and 42 children with febrile seizure. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology, which is currently applied in many fields of biological and medical sciences. Diagnosis was made by at least two pediatric neurologists based on the clinical findings and routine examinations. All specimens were collected for diagnostic tests and the remaining portion of the specimens were used for the SELDI-TOF MS investigations.</p> <p>Results</p> <p>In experiment 1, CSF from patients with febrile seizures (n = 28), patients with encephalopathy (n = 8) (including influenza encephalopathy (n = 3), encephalopathy due to rotavirus (n = 1), human herpes virus 6 (n = 1)) were used for the SELDI analysis. In experiment 2, SELDI analysis was performed on CSF from a second set of febrile seizure patients (n = 14) and encephalopathy patients (n = 5). We found that the peak with an m/z of 4810 contributed the most to the separation of the two groups. After purification and identification of the 4.8-kDa protein, a 4.8-kDa proteolytic peptide fragment from the neurosecretory protein VGF precursor (VGF4.8) was identified as a novel biomarker for encephalopathy.</p> <p>Conclusions</p> <p>Expression of VGF4.8 has been reported to be decreased in pathologically degenerative changes such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and encephalopathy. Thus, the VGF4.8 peptide might be a novel marker for degenerative brain conditions.</p

Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor-21

OBJECTIVE—Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator–activator receptor (PPAR) –dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPAR, might modify FGF-21 levels. RESEARCH DESIGN AND METHODS—The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPAR activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS—Oleate and linoleate increased FGF-21 expression and secretion in a PPAR-dependent fashion, as demonstrated by small-interfering RNA–induced PPAR knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect. CONCLUSIONS—The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity

Infection with Mansonella perstans Nematodes in Buruli Ulcer Patients, Ghana.

During August 2010-December 2012, we conducted a study of patients in Ghana who had Buruli ulcer, caused by Mycobacterium ulcerans, and found that 23% were co-infected with Mansonella perstans nematodes; 13% of controls also had M. perstans infection. M. perstans co-infection should be considered in the diagnosis and treatment of Buruli ulcer