Performing vaginal lavage, crystal violet staining, and vaginal cytological evaluation for mouse estrous cycle staging identification

A rapid means of assessing reproductive status in rodents is useful not only in the study of reproductive dysfunction but is also required for the production of new mouse models of disease and investigations into the hormonal regulation of tissue degeneration (or regeneration) following pathological challenge. The murine reproductive (or estrous) cycle is divided into 4 stages: proestrus, estrus, metestrus, and diestrus. Defined fluctuations in circulating levels of the ovarian steroids 17-β-estradiol and progesterone, the gonadotropins luteinizing and follicle stimulating hormones, and the luteotropic hormone prolactin signal transition through these reproductive stages. Changes in cell typology within the murine vaginal canal reflect these underlying endocrine events. Daily assessment of the relative ratio of nucleated epithelial cells, cornified squamous epithelial cells, and leukocytes present in vaginal smears can be used to identify murine estrous stages. The degree of invasiveness, however, employed in collecting these samples can alter reproductive status and elicit an inflammatory response that can confound cytological assessment of smears. Here, we describe a simple, non-invasive protocol that can be used to determine the stage of the estrous cycle of a female mouse without altering her reproductive cycle. We detail how to differentiate between the four stages of the estrous cycle by collection and analysis of predominant cell typology in vaginal smears and we show how these changes can be interpreted with respect to endocrine status

A noninvasive hemoglobin monitor in the pediatric intensive care unit

Background Critically ill pediatric patients frequently require hemoglobin monitoring. Accurate noninvasive Hb (SpHb) would allow practitioners to decrease anemia from repeated blood draws, traumatic blood draws, and a decreased number of laboratory Hb (LabHb) medical tests. The Food and Drug Administration has approved the Masimo Pronto SpHb and associated Rainbow probes; however, its use in the pediatric intensive care unit (PICU) is controversial. In this study, we define the degree of agreement between LabHb and SpHb using the Masimo Pronto SpHb Monitor and identify clinical and demographic conditions associated with decreased accuracy. Materials and methods We performed a prospective, observational study in a large PICU at an academic medical center. Fifty-three pediatric patients (30-d and 18-y-old), weighing >3 kg, admitted to the PICU from January-April 2013 were examined. SpHb levels measured at the time of LabHb blood draw were compared and analyzed. Results Only 83 SpHb readings were obtained in 118 attempts (70.3%) and 35 readings provided a result of "unable to obtain." The mean LabHb and SpHb were 11.1 g/dL and 11.2 g/dL, respectively. Bland-Altman analysis showed a mean difference of 0.07 g/dL with a standard deviation of ±2.59 g/dL. Pearson correlation is 0.55, with a 95% confidence interval between 0.38 and 0.68. Logistic regression showed that extreme LabHb values, increasing skin pigmentation, and increasing body mass index were predictors of poor agreement between SpHb and LabHb (P < 0.05). Separately, increasing body mass index, hypoxia, and hypothermia were predictors for undetectable readings (P < 0.05). Conclusions The Masimo Pronto SpHb Monitor provides adequate agreement for the trending of hemoglobin levels in critically ill pediatric patients. However, the degree of agreement is insufficient to be used as the sole indicator for transfusion decisions and should be used in context of other clinical parameters to determine the need for LabHb in critically ill pediatric patients

Fungicide resistance management in Australian grain crops

Fungicide resistance is a serious and increasing problem in cropping systems worldwide. Fungicides are an important component of integrated disease management strategies for the protection of crops from the impacts of fungal diseases. However, as their use has increased, the effectiveness of some fungicides has been reduced by the development of fungicide resistant pathogen populations. Without intervention, more fungicides are likely to become ineffective

Targeting malaria parasites with novel derivatives of azithromycin

Introduction: The spread of artemisinin resistant Plasmodium falciparum parasites is of global concern and highlights the need to identify new antimalarials for future treatments. Azithromycin, a macrolide antibiotic used clinically against malaria, kills parasites via two mechanisms: ‘delayed death’ by inhibiting the bacterium-like ribosomes of the apicoplast, and ‘quick-killing’ that kills rapidly across the entire blood stage development. Methods: Here, 22 azithromycin analogues were explored for delayed death and quick-killing activities against P. falciparum (the most virulent human malaria) and P. knowlesi (a monkey parasite that frequently infects humans). Results: Seventeen analogues showed improved quick-killing against both Plasmodium species, with up to 38 to 20-fold higher potency over azithromycin after less than 48 or 28 hours of treatment for P. falciparum and P. knowlesi, respectively. Quick-killing analogues maintained activity throughout the blood stage lifecycle, including ring stages of P. falciparum parasites (5-fold more selective against P. falciparum than human cells. Isopentenyl pyrophosphate supplemented parasites that lacked an apicoplast were equally sensitive to quick-killing analogues, confirming that the quick killing activity of these drugs was not directed at the apicoplast. Further, activity against the related apicoplast containing parasite Toxoplasma gondii and the gram-positive bacterium Streptococcus pneumoniae did not show improvement over azithromycin, highlighting the specific improvement in antimalarial quick-killing activity. Metabolomic profiling of parasites subjected to the most potent compound showed a build-up of non-haemoglobin derived peptides that was similar to chloroquine, while also exhibiting accumulation of haemoglobin-derived peptides that was absent for chloroquine treatment. Discussion: The azithromycin analogues characterised in this study expand the structural diversity over previously reported quick-killing compounds and provide new starting points to develop azithromycin analogues with quickkilling antimalarial activity.Amy L. Burns, Brad E. Sleebs, Maria Gancheva, Kimberley T. McLean, Ghizal Siddiqui, Henrietta Venter, James G. Beeson, Ryan O, Handley, Darren J. Creek, Shutao Ma, Sonja Frölich, Christopher D. Goodman, Geoffrey I. McFadden, and Danny W. Wilso

In memoriam mr. sc. Vesna Burić (1943. - 2002.)

The exceptionally organic-rich rocks of the 1.98 Ga Zaonega Formation deposited in the Onega Basin, NW Russia, have refined our understanding of Earth System evolution during the Paleoproterozoic rise in atmospheric oxygen. These rocks were formed in vent- or seep influenced settings contemporaneous with voluminous mafic volcanism and contain strongly 13C-depleted organic matter. Here we report new isotopic (δ34S, Δ33S, Δ36S, δ13Corg) and mineralogical, major element, total sulphur and organic carbon data for the upper part of the Zaonega Formation, which was deposited shortly after the termination of the Lomagundi-Jatuli positive carbon isotope excursion. The data were collected on a recently obtained 102 m drillcore section and show a δ13Corg shift from -38‰ to -25‰. Sedimentary sulphides have δ34S values typically between +15‰ and +25‰ reflecting closed-system sulphur isotope behaviour driven by high rates of microbial sulphate reduction, high sulphate demand, hydrothermal activity and hydrocarbon seepage. Four intervals record δ34S values that exceed +30‰. We interpret these unusually 34S-enriched sulphides to be a result of limited sulfate diffusion into pore waters due to changes in sedimentation and/or periods of basinal restriction. Additionally, there are four negative δ34S and positive Δ33S excursions that are interpreted to reflect changes in the open/closed-system behaviour of sulphate reduction or availability of reactive iron. Our findings highlight the influence of basinal processes in regulating sulphur isotope records and the need for care before interpreting such signals as reflecting global conditions

Modeling infectious disease dynamics in the complex landscape of global health.

Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational, and spatial scales, which span hours to months, cells to ecosystems, and local to global spread. Moreover, some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity and changeable human behavior, elevate prevention and control from matters of national policy to international challenge. In the face of this complexity, mathematical models offer valuable tools for synthesizing information to understand epidemiological patterns, and for developing quantitative evidence for decision-making in global health

Measurement of the Mass Splittings between the bbˉχb,J(1P)b\bar{b}\chi_{b,J}(1P) States

We present new measurements of photon energies and branching fractions for the radiative transitions: Upsilon(2S)->gamma+chi_b(J=0,1,2). The masses of the chi_b states are determined from the measured radiative photon energies. The ratio of mass splittings between the chi_b substates, r==(M[J=2]-M[J=1])/(M[J=1]-M[J=0]) with M the chi_b mass, provides information on the nature of the bbbar confining potential. We find r(1P)=0.54+/-0.02+/-0.02. This value is in conflict with the previous world average, but more consistent with the theoretical expectation that r(1P)<r(2P); i.e., that this mass splittings ratio is smaller for the chi_b(1P) triplet than for the chi_b(2P) triplet.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

The roles of the formal and informal sectors in the provision of effective science education

For many years, formal school science education has been criticised by students, teachers, parents and employers throughout the world. This article presents an argument that a greater collaboration between the formal and the informal sector could address some of these criticisms. The causes for concern about formal science education are summarised and the major approaches being taken to address them are outlined. The contributions that the informal sector currently makes to science education are identified. It is suggested that the provision of an effective science education entails an enhanced complementarity between the two sectors. Finally, there is a brief discussion of the collaboration and communication still needed if this is to be effective