Airway exposure to multi-walled carbon nanotubes disrupts the female reproductive cycle without affecting pregnancy outcomes in mice

Abstract Background The use of multiwalled carbon nanotubes (MWCNT) is increasing due to a growing use in a variety of products across several industries. Thus, occupational exposure is also of increasing concern, particularly since airway exposure to MWCNTs can induce sustained pulmonary acute phase response and inflammation in experimental animals, which may affect female reproduction. This proof-of-principle study therefore aimed to investigate if lung exposure by intratracheal instillation of the MWCNT NM-400 would affect the estrous cycle and reproductive function in female mice. Results Estrous cycle regularity was investigated by comparing vaginal smears before and after exposure to 67 μg of NM-400, whereas reproductive function was analyzed by measuring time to delivery of litters after instillation of 2, 18 or 67 μg of NM-400. Compared to normal estrous cycling determined prior to exposure, exposure to MWCNT significantly prolonged the estrous cycle during which exposure took place, but significantly shortened the estrous cycle immediately after the exposed cycle. No consistent effects were seen on time to delivery of litter or other gestational or litter parameters, such as litter size, sex ratio, implantations and implantation loss. Conclusion Lung exposure to MWCNT interfered with estrous cycling. Effects caused by MWCNTs depended on the time of exposure: the estrous stage was particularly sensitive to exposure, as animals exposed during this stage showed a higher incidence of irregular cycling after exposure. Our data indicates that MWCNT exposure may interfere with events leading to ovulation

The usefulness of rapid diagnostic tests in the new context of low malaria transmission in zanzibar.

BACKGROUND\ud \ud We assessed if histidine-rich-protein-2 (HRP2) based rapid diagnostic test (RDT) remains an efficient tool for Plasmodium falciparum case detection among fever patients in Zanzibar and if primary health care workers continue to adhere to RDT results in the new epidemiological context of low malaria transmission. Further, we evaluated the performance of RDT within the newly adopted integrated management of childhood illness (IMCI) algorithm in Zanzibar.\ud \ud METHODS AND FINDINGS\ud \ud We enrolled 3890 patients aged ≥2 months with uncomplicated febrile illness in this health facility based observational study conducted in 12 primary health care facilities in Zanzibar, between May-July 2010. One patient had an inconclusive RDT result. Overall 121/3889 (3.1%) patients were RDT positive. The highest RDT positivity rate, 32/528 (6.1%), was found in children aged 5-14 years. RDT sensitivity and specificity against PCR was 76.5% (95% CI 69.0-83.9%) and 99.9% (95% CI 99.7-100%), and against blood smear microscopy 78.6% (95% CI 70.8-85.1%) and 99.7% (95% CI 99.6-99.9%), respectively. All RDT positive, but only 3/3768 RDT negative patients received anti-malarial treatment. Adherence to RDT results was thus 3887/3889 (99.9%). RDT performed well in the IMCI algorithm with equally high adherence among children <5 years as compared with other age groups.\ud \ud CONCLUSIONS\ud \ud The sensitivity of HRP-2 based RDT in the hands of health care workers compared with both PCR and microscopy for P. falciparum case detection was relatively low, whereas adherence to test results with anti-malarial treatment was excellent. Moreover, the results provide evidence that RDT can be reliably integrated in IMCI as a tool for improved childhood fever management. However, the relatively low RDT sensitivity highlights the need for improved quality control of RDT use in primary health care facilities, but also for more sensitive point-of-care malaria diagnostic tools in the new epidemiological context of low malaria transmission in Zanzibar.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT01002066

The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 95\% CI: 0.56, 1.17 p = 0.24). Most children (76.0\%) tested positive by reference mRDT, but many were not prescribed AL (22.5\% intervention versus 25.9\% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3\% invention vs 42.4\% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management

Type-i Optical Emissions In Gesi Quantum Dots

The authors studied the optical emission of GeSi quantum dots under externally applied biaxial stress using samples grown with different temperatures varying from 430 to 700 °C. The optical emission energy of samples grown at low temperatures is rather insensitive to the applied external stress, consistent with the type-II band alignment. However, for samples grown at high temperatures we observed a large blueshift, which suggests type-I alignment. The result implies that recombination strength can be controlled by the growth temperature, which can be useful for optical device applications. © 2007 American Institute of Physics.915Brunner, K., (2002) Rep. Prog. Phys., 65, p. 27Medeiros-Ribeiro, G., Bratkovski, A.M., Kamins, T.I., Ohlbert, D.A.A., Williams, R.S., (1998) Science, 279, p. 353Wan, J., Jin, G.L., Jiang, Z.M., Luo, Y.H., Liu, J.L., Wang, K.L., (2001) Appl. Phys. Lett., 78, p. 1763El Kurdi, M., Sauvage, S., Fishman, G., Boucaud, P., (2006) Phys. Rev. B, 73, p. 195327Yakimov, A.I., Dvurechenskii, A.V., Nikiforov, A.I., Bloshkin, A.A., Nenashev, A.V., Volodin, V.A., (2006) Phys. Rev. B, 73, p. 115333Dashiell, M.W., Denker, U., Müller, C., Costantini, G., Manzano, C., Kern, K., Schmidt, O.G., (2002) Appl. Phys. Lett., 80, p. 1279Larsson, M., Elfving, A., Holtz, P.O., Hansson, G.V., Ni, W.-X., (2003) Appl. Phys. Lett., 82, p. 4785Thewalt, M.L.W., Harrison, D.A., Reinhart, C.F., Wolk, J.A., Lafontaine, H., (1997) Phys. Rev. Lett., 79, p. 269Larsson, M., Elfving, A., Ni, W.-X., Hansson, G.V., Holtz, P.O., (2006) Phys. Rev. B, 73, p. 195319Schmidt, O.G., Eberl, K., (2000) Phys. Rev. B, 62, p. 16715Tudury, H.A.P., Nakaema, M.K.K., Iikawa, F., Brum, J.A., Ribeiro, E., Carvalho Jr., W., Bernussi, A.A., Gobbi, A.L., (2001) Phys. Rev. B, 64, p. 153301Gomes, P.F., Godoy, M.P.F., Nakaema, M.K.K., Iikawa, F., Lamas, T.E., Quivy, A.A., Brum, J.A., (2004) Phys. Status Solidi C, 3, p. 547De Godoy, M.P.F., Nakaema, M.K.K., Iikawa, F., Carvalho Jr. Wilson, Evaldo, R., Gobbi, A.L., (2004) Rev. Sci. Instrum., 75, p. 194

A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants in Relation to Risk of Type 1 Diabetes

BACKGROUND: The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes. METHODOLOGY/ PRINCIPAL FINDINGS: The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p'-DDE (OR 0.56, 95% CI 0.29, 1.08). CONCLUSIONS: The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes

Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis

Key messages Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.Peer reviewe

Painleve I, Coverings of the Sphere and Belyi Functions

The theory of poles of solutions of Painleve-I is equivalent to the Nevanlinna problem of constructing a meromorphic function ramified over five points - counting multiplicities - and without critical points. We construct such meromorphic functions as limit of rational ones. In the case of the tritronquee solution these rational functions are Belyi functions.Comment: 33 pages, many figures. Version 2: minor corrections and minor changes in the bibliograph

Psychosocial factors associated with change in pain and disability outcomes in chronic low back pain patients treated by physiotherapist: a systematic review

Background: Almost 80% of people have low back pain at least once in their life. Clinical guidelines emphasize the use of conservative physiotherapy and the importance of staying active. While the psychological factors predicting poor recovery following surgical intervention are understood, the psychosocial factors associated with poor outcomes following physiotherapy have yet to be identified. Methods: Electronic searches of PubMed, Medline, CINAHL, PsycINFO and EBSCO were conducted using terms relating to psychosocial factors, chronic low back pain, disability and physiotherapy. Papers examining the relationship between psychosocial factors and pain and disability outcomes following physiotherapy were included. Two reviewers selected, appraised and extracted studies independently. Results: In total, 10 observational studies were identified that suggested an association between fear of movement, depression, self-efficacy and catastrophizing in modifying pain and disability outcomes following physiotherapy. Discussion: Although limited by methodological shortcomings of included studies, and heterogeneity of physiotherapy interventions and measures of disability and psychosocial outcomes, the findings are consistent with other research in the context of back pain and physiotherapy, which suggest an association between psychosocial factors, including fear of movement, catastrophizing and self-efficacy and pain and disability outcomes in chronic low back pain patients treated by physiotherapist. However, a direct relationship cannot be concluded from this study. Conclusion: Findings suggest an association between psychosocial factors, including fear of movement, catastrophizing and self-efficacy and pain and disability outcomes in chronic low back pain patients treated by physiotherapist, which warrants further study