Beyond the microcirculation: sequestration of infected red blood cells and reduced flow in large draining veins in experimental cerebral malaria.

Sequestration of infected red blood cells (iRBCs) in the microcirculation is a hallmark of cerebral malaria (CM) in post-mortem human brains. It remains controversial how this might be linked to the different disease manifestations, in particular brain swelling leading to brain herniation and death. The main hypotheses focus on iRBC-triggered inflammation and mechanical obstruction of blood flow. Here, we test these hypotheses using murine models of experimental CM (ECM), SPECT-imaging of radiolabeled iRBCs and cerebral perfusion, MR-angiography, q-PCR, and immunohistochemistry. We show that iRBC accumulation and reduced flow precede inflammation. Unexpectedly, we find that iRBCs accumulate not only in the microcirculation but also in large draining veins and sinuses, particularly at the rostral confluence. We identify two parallel venous streams from the superior sagittal sinus that open into the rostral rhinal veins and are partially connected to infected skull bone marrow. The flow in these vessels is reduced early, and the spatial patterns of pathology correspond to venous drainage territories. Our data suggest that venous efflux reductions downstream of the microcirculation are causally linked to ECM pathology, and that the different spatiotemporal patterns of edema development in mice and humans could be related to anatomical differences in venous anatomy.

Smart Nanozymes for Cancer Therapy: The Next Frontier in Oncology.

Nanomaterials that mimic the catalytic activity of natural enzymes in the complex biological environment of the human body are called nanozymes. Recently, nanozyme systems have been reported with diagnostic, imaging, and/or therapeutic capabilities. Smart nanozymes strategically exploit the tumor microenvironment (TME) by the in situ generation of reactive species or by the modulation of the TME itself to result in effective cancer therapy. This topical review focuses on such smart nanozymes for cancer diagnosis, and therapy modalities with enhanced therapeutic effects. The dominant factors that guide the rational design and synthesis of nanozymes for cancer therapy include an understanding of the dynamic TME, structure-activity relationships, surface chemistry for imparting selectivity, and site-specific therapy, and stimulus-responsive modulation of nanozyme activity. This article presents a comprehensive analysis of the subject including the diverse catalytic mechanisms of different types of nanozyme systems, an overview of the TME, cancer diagnosis, and synergistic cancer therapies. The strategic application of nanozymes in cancer treatment can well be a game changer in future oncology. Moreover, recent developments may pave the way for the deployment of nanozyme therapy into other complex healthcare challenges, such as genetic diseases, immune disorders, and ageing.

Multistate Comparison of Attractants and the Impact of Fruit Development Stage on Trapping Drosophila suzukii (Diptera: Drosophilidae) in Raspberry and Blueberry.

Spotted-wing drosophila, Drosophila suzukii Matsumura (Diptera: Drosophilidae), is an invasive pest of soft-skinned fruits across the globe. Effective monitoring is necessary to manage this pest, but suitable attractants are still being identified. In this study, we combined lures with fermenting liquid baits to improve D. suzukii trapping specificity and attractiveness. We also measured the efficiency and specificity of baits/lures during different times of the season; the reproductive status of females among baits/lures; and the effects of locations and crop type on these response variables. We developed a metric that combined mating status and fat content to determine differences in types of females attracted. Lures utilizing yeast and sugar-based volatiles trapped the most D. suzukii. The addition of a commercial lure to yeast and sugar-based lures increased catches in most locations, but was also the least specific to D. suzukii. Apple juice-based chemical lures tended to be most specific to D. suzukii, while lures comprised of a singular attractant tended to trap more D. suzukii with a higher reproductive potential than combinations of attractants. Trap catch and lure specificity was lower during fruit development than fruit ripening. While catch amounts varied by geographic location and crop type, attractants performed similarly relative to each other in each location and crop. Based on the metrics in this study, the yeast and sugar-based attractants were the most effective lures. However, further work is needed to improve early season monitoring, elucidate the effects of physiological status on bait attraction, and understand how abiotic factors influence bait attraction.

Evaluation of Off-season Potential Breeding Sources for Spotted Wing Drosophila (Drosophila suzukii Matsumura) in Michigan.

It has been suggested that fruit wastes including dropped and unharvested fruits, and fruit byproducts (i.e., pomace) found in fruit plantings and cideries or wine-making facilities could serve as potential off-season breeding sites for spotted wing Drosophila (Drosophila suzukii Matsumura (Diptera: Drosophilidae)). This idea, however, has yet to be widely tested. The goal of our study was to determine the potential of dropped fruit and fruit wastes as Fall spotted wing Drosophila breeding resources in Michigan, USA. Fruit waste samples were collected from 15 farms across the lower peninsula of Michigan and were evaluated for spotted wing Drosophila and other drosophilid emergence and used in host suitability bioassays. All of the dropped apples, pears, grapes, and raspberries and 40% of apple and 100% of grape fruit pomace evaluated were found to contain spotted wing Drosophila with the highest numbers collected from dropped grapes and pears. Greater spotted wing Drosophila recovery was found in fruit wastes at sites attached with cideries and wine-making facilities and with multiple cultivated fruit crops than sites with no cideries and only one crop. Females oviposited in raspberry, pear, apple, grape, apple pomace and grape pomace samples with the highest rates of reproduction in raspberries. Our results demonstrate that fruit wastes including dropped berry, pomme and stone fruits, as well as fruit compost may be important late season reproductive resources for spotted wing Drosophila.

Lateral Dispersal and Foraging Behavior of Entomopathogenic Nematodes in the Absence and Presence of Mobile and Non-Mobile Hosts.

Entomopathogenic nematodes have been classified into cruisers (active searchers) and ambushers (sit and wait foragers). However, little is known about their dispersal and foraging behavior at population level in soil. We studied lateral dispersal of the ambush foraging Steinernema carpocapsae (ALL strain) and cruise foraging Heterorhabditis bacteriophora (GPS11 strain) from infected host cadavers in microcosms (0.05 m2) containing Wooster silt-loam soil (Oxyaquic fragiudalf) and vegetation in the presence or absence of non-mobile and mobile hosts. Results showed that the presence of a non-mobile host (Galleria mellonella larva in a wire mesh cage) enhanced H. bacteriophora dispersal for up to 24 hr compared with no-host treatment, but had no impact on S. carpocapsae dispersal. In contrast, presence of a mobile host (G. mellonella larvae) increased dispersal of S. carpocapsae compared with no host treatment, but had no effect on H. bacteriophora dispersal. Also H. bacteriophora was better at infecting non-mobile than mobile hosts released into the microcosms and S. carpocapsae was better at infecting mobile than non-mobile hosts, thus affirming the established cruiser-ambusher theory. However, results also revealed that a large proportion of infective juveniles (IJs) of both species stayed near (≤ 3.8 cm) the source cadaver (88-96% S. carpocapsae; 67-79% H. bacteriophora), and the proportion of IJs reaching the farthest distance (11.4 cm) was significantly higher for S. carpocapsae (1.4%) than H. bacteriophora (0.4%) in the presence of mobile hosts. S. carpocapsae also had higher average population displacement than H. bacteriophora in the presence of both the non-mobile (5.07 vs. 3.6 cm/day) and mobile (8.06 vs. 5.3 cm/day) hosts. We conclude that the two species differ in their dispersal and foraging behavior at the population level and this behavior is affected by both the presence and absence of hosts and by their mobility.

Ambush foraging entomopathogenic nematodes employ 'sprinters' for long-distance dispersal in the absence of hosts.

Ambush foragers must employ a long-distance dispersal strategy to maximize reproductive success in the absence of hosts. This hypothesis was tested by comparing lateral dispersal of the ambusher, Steinernema carpocapsae , and the cruiser, Heterorhabditis bacteriophora , nematodes from infected host cadavers in autoclaved, silt-loam soil in large microcosms (0.05-1.5 m(2)) with or without vegetation in the absence of hosts. Dispersal was estimated by taking soil cores (5 × 2 cm in diameter) from the microcosms at different intervals (6-240 hr) and distances (3.8-61 cm) from the infected host cadavers and baiting with Galleria mellonella larvae. The numbers of baited larvae killed and the numbers of infective juveniles (IJs) penetrated in dead baits were counted to compute the percentage of IJs dispersed from the source cadavers, based on the emergence potential and penetration efficiency of the 2 species, and analyzed. Vegetation enhanced dispersal of both species but more so for H. bacteriophora . Although the pattern of dispersal differed spatio-temporally for the 2 species, average population displacement was similar (∼6 cm/day). A majority of the S. carpocapsae population ambushed close to the source cadaver (<3.8 cm), whereas a majority of H. bacteriophora population dispersed between 7-12 cm away from the source cadaver. About 4% of the S. carpocapsae population dispersed faster than the fastest H. bacteriophora , reaching 30-61 cm, compared to only 2% of the H. bacteriophora population dispersing this far. This use of 'sprinters' for long-distance dispersal may represent an adaptive dispersal strategy by the otherwise ambush forager S. carpocapsae in the absence of hosts.

Atypical presentations of multiple evanescent white dot syndrome without white dots: a case series.

PURPOSE: To describe three unusual clinical cases of patients who were diagnosed with multiple evanescent white dot syndrome at the onset of their disease but lacked the characteristic white dots on clinical examination, autofluorescence, and angiographic testing at any time during their follow-up. METHODS: Three eyes of three patients with clinical symptoms of multiple evanescent white dot syndrome seen at an academic clinical practice were included. Retinal imaging, including fluorescein angiography, indocyanine green imaging, fundus autofluorescence, and optical coherence tomography, was used to further characterize and describe the clinical findings. RESULTS: All three patients presented with classic multiple evanescent white dot syndrome complaints. All patients demonstrated classic foveal granularity and mild disk swelling and/or peripapillary whitening. No characteristic hyperfluorescent lesions were seen on fluorescein angiography, and indocyanine green imaging did not demonstrate typical patterns of hypofluorescence and/or leakage. Optical coherence tomography documented focal disruption or loss of the inner segment/outer segment photoreceptor line in all cases. CONCLUSION: Our case series demonstrates another atypical presentation of multiple evanescent white dot syndrome that has not been described previously: foveal involvement at the onset of the disease without white spots.

Pressure alopecia following vitreoretinal surgery.

PURPOSE: To describe a patient with pressure alopecia following vitreoretinal surgery. DESIGN: Case report. METHODS: An 11-year-old boy underwent vitreoretinal surgery for left retinal detachment. One week postoperatively, his parents noticed a patch of alopecia where his head may have been in contact with the wrist-rest assembly placed around the head during the surgical procedure. RESULTS: Pressure alopecia on the parieto-occipital region of the scalp was observed. Hair regrowth occurred during the follow-up visits. CONCLUSION: Pressure alopecia is a rare complication of lengthy surgery and is underrecognized in ophthalmic practice. Precautions should be taken to avoid this preventable complication.