The effect of maternal protein restriction during perinatal life on the inflammatory response in pediatric rats

Fetal growth restriction can affect health outcomes in postnatal life. This study tested the hypothesis that the response to an inflammatory pulmonary insult is altered in pediatric fetal growth restricted rats. Using a low-protein diet during gestation and postnatal life, growth-restricted male and female rats and healthy control rats were exposed to an inflammatory insult via the intratracheal instillation of heat-killed bacteria. After 6 h, animal lungs were examined for lung inflammation and status of the surfactant system. The results showed that in response to an inflammatory insult, neutrophil infiltration was decreased in both male and female rats in the growth-restricted animals compared with the control rats. The amount of surfactant was increased in the growth-restricted animals compared with the control rats, regardless of the inflammatory insult. It is concluded that fetal growth restriction results in increased surfactant and altered neutrophil responses following pulmonary insult

Trachoma

Trachoma is a neglected tropical disease caused by infection with conjunctival strains of Chlamydia trachomatis. It can result in blindness. Pathophysiologically, trachoma is a disease complex composed of two linked chronic processes: a recurrent, generally subclinical infectious–inflammatory disease that mostly affects children, and a non-communicable, cicatricial and, owing to trichiasis, eventually blinding disease that supervenes in some individuals later in life. At least 150 infection episodes over an individual’s lifetime are needed to precipitate trichiasis; thus, opportunity exists for a just global health system to intervene to prevent trachomatous blindness. Trachoma is found at highest prevalence in the poorest communities of low-income countries, particularly in sub-Saharan Africa; in June 2021, 1.8 million people worldwide were going blind from the disease. Blindness attributable to trachoma can appear in communities many years after conjunctival C. trachomatis transmission has waned or ceased; therefore, the two linked disease processes require distinct clinical and public health responses. Surgery is offered to individuals with trichiasis and antibiotic mass drug administration and interventions to stimulate facial cleanliness and environmental improvement are designed to reduce infection prevalence and transmission. Together, these interventions comprise the SAFE strategy, which is achieving considerable success. Although much work remains, a continuing public health problem from trachoma in the year 2030 will be difficult for the world to excuse

Gravitational Lensing at Millimeter Wavelengths

With today's millimeter and submillimeter instruments observers use gravitational lensing mostly as a tool to boost the sensitivity when observing distant objects. This is evident through the dominance of gravitationally lensed objects among those detected in CO rotational lines at z>1. It is also evident in the use of lensing magnification by galaxy clusters in order to reach faint submm/mm continuum sources. There are, however, a few cases where millimeter lines have been directly involved in understanding lensing configurations. Future mm/submm instruments, such as the ALMA interferometer, will have both the sensitivity and the angular resolution to allow detailed observations of gravitational lenses. The almost constant sensitivity to dust emission over the redshift range z=1-10 means that the likelihood for strong lensing of dust continuum sources is much higher than for optically selected sources. A large number of new strong lenses are therefore likely to be discovered with ALMA, allowing a direct assessment of cosmological parameters through lens statistics. Combined with an angular resolution <0.1", ALMA will also be efficient for probing the gravitational potential of galaxy clusters, where we will be able to study both the sources and the lenses themselves, free of obscuration and extinction corrections, derive rotation curves for the lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on "Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be published by Springer-Verlag 2002. Paper with full resolution figures can be found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g

Pre-M Phase-promoting Factor Associates with Annulate Lamellae in Xenopus Oocytes and Egg Extracts

We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates

Moral courage in the workplace: moving to and from the desire and decision to act

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72135/1/j.1467-8608.2007.00484.x.pd

Exploring water, sanitation, and hygiene coverage targets for reaching and sustaining trachoma elimination: G-computation analysis

BACKGROUND: Trachoma is the leading infectious cause of blindness. To reduce transmission, water, sanitation, and hygiene (WaSH) improvements are promoted through a comprehensive public health strategy. Evidence supporting the role of WaSH in trachoma elimination is mixed and it remains unknown what WaSH coverages are needed to effectively reduce transmission. METHODS/FINDINGS: We used g-computation to estimate the impact on the prevalence of trachomatous inflammation-follicular among children aged 1-9 years (TF1-9) when hypothetical WaSH interventions raised the minimum coverages from 5% to 100% for "nearby" face-washing water (<30 minutes roundtrip collection time) and adult latrine use in an evaluation unit (EU). For each scenario, we estimated the generalized prevalence difference as the TF1-9 prevalence under the intervention scenarios minus the observed prevalence. Data from 574 cross-sectional surveys conducted in 16 African and Eastern Mediterranean countries were included. Surveys were conducted from 2015-2019 with support from the Global Trachoma Mapping Project and Tropical Data. When modeling interventions among EUs that had not yet met the TF1-9 elimination target, increasing nearby face-washing water and latrine use coverages above 30% was generally associated with consistent decreases in TF1-9. For nearby face-washing water, we estimated a ≥25% decrease in TF1-9 at 65% coverage, with a plateau upon reaching 85% coverage. For latrine use, the estimated decrease in TF1-9 accelerated from 80% coverage upward, with a ≥25% decrease in TF1-9 by 85% coverage. Among EUs that had previously met the elimination target, results were inconclusive. CONCLUSIONS: Our results support Sustainable Development Goal 6 and provide insight into potential WaSH-related coverage targets for trachoma elimination. Targets can be tested in future trials to improve evidence-based WaSH guidance for trachoma

Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease

Background: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. Methods: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. Results: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Conclusions: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM