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Third, the Spanish flu killed approximately 17 to 50 million people, and the lack of human response, overcrowding, and poor hygiene were key in promoting the spread and high mortality. Human behavior is the most important strategy for preventing the virus spread and we must adhere to proper precautions. This review will cover our current understanding of the pathology and treatment for COVID-19 and highlight similarities between past pandemics. By revisiting history, we hope to emphasize the importance of human behavior and innovative therapies as we wait for the development of a vaccine. Graphical Abstract.
This study sought to assess ocular surface disease changes following cataract surgery combined with trabecular micro-bypass stent(s) implantation (iStent or iStent inject).
This prospective interventional single-arm clinical trial enrolled 47 eyes with mild-to-moderate open-angle glaucoma (OAG) on 1-4 glaucoma medications who underwent phacoemulsification and trabecular micro-bypass stent(s) implantation. Key glaucoma and ocular surface data through 3months postoperatively included the Ocular Surface Disease Index score (OSDI), corneal/conjunctival staining (Oxford Schema), fluorescein tear break-up time (FTBUT), conjunctival hyperemia (Efron Scale), glaucoma medications, and intraocular pressure (IOP).
Mean OSDI scores improved from 40.1 ± 21.6 (severe) preoperatively to 17.5 ± 15.3 (mild) at 3months (p < 0.0001). While 73% of eyes had moderate or severe OSDI scores preoperatively, 29% had such scores at 3months, and the OSDI score was normal in 57% of eyes versus 9% preoperatively. PHA767491 Mean FTBUT increased from 4.3 ± 2.4s preoperatively to 6.4 ± 2.5s at 3months (p < 0.0001); mean Oxford corneal/conjunctival staining reduced from 1.4 ± 1.0 preoperatively to 0.4 ± 0.6 at 3months (p < 0.0001); mean Efron conjunctival hyperemia score reduced from 1.4 ± 0.7 preoperatively to 1.2 ± 0.6 at 3months (p = 0.118). The number of glaucoma medications decreased from 1.5 ± 0.9 to 0.6 ± 0.8 mean medications (60% reduction, p < 0.0001), with all eyes maintaining or reducing medications versus preoperatively and 55% of eyes becoming medication-free (versus 0% preoperatively). Mean IOP reduced from 17.4 ± 4.2mmHg to 14.5 ± 3.2mmHg (p < 0.0001). The safety profile was excellent.
Implantation of trabecular micro-bypass stent(s) (iStent or iStent inject) with cataract surgery produced significant improvements in ocular surface health, alongside significant reductions in IOP and medications.
ClinicalTrials.gov identifier, NCT04452279.
ClinicalTrials.gov identifier, NCT04452279.
Despite of classically acting as definitive hosts of different Sarcocystis species, domestic cats have been pointed out as possible intermediate hosts of S. neurona and S. felis. Nonetheless, details concerning natural sarcocyst development in cats without Sarcocystis-associated disease are scarce. This study aimed to characterize the natural occurrence of muscular sarcocysts in a random group of cats submitted for necropsy.
One hundred cats necropsied at a Veterinary Pathology Service were included. Nine different muscular tissues from each cat were sampled for histological analysis and Polymerase Chain Reaction (PCR) using multispecies primers for Sarcocystis neurona, Neospora caninum and Toxoplasma gondii. PCR-positive cases were sequenced for genus and species identification. Epidemiologic data was also analyzed.
Tissue sarcocysts were identified in hematoxylin and eosin-stained slides from five cats, and S. neurona was the only confirmed species. Multifocal sarcocysts affecting two or more muscles were common among positive cats (4/5). Sarcocysts were identified within vastus lateralis (3/5), intercostal (3/5), subscapular (2/5) and diaphragm (2/5) sections. These cysts were always incidental necropsy findings. All sarcocyst-positive cats were from urban areas, among which two were feral and three were pets. Outdoor access was consistently reported. Two cats were positive for retrovirosis, and treatments with potentially immunosuppressive drugs were never stated.
This study describes the natural occurrence of S. neurona muscular sarcocysts in a random group of cats without Sarcocystis-associated disease. These findings reinforce the participation of feral and pet cats from urban areas as natural intermediate hosts of S. neurona.
This study describes the natural occurrence of S. neurona muscular sarcocysts in a random group of cats without Sarcocystis-associated disease. These findings reinforce the participation of feral and pet cats from urban areas as natural intermediate hosts of S. neurona.β-lapachone (β-lap) is reduced in tumor cells by the enzyme NAD(P)H quinone acceptor oxidoreductase 1 (NQO1) to a labile hydroquinone which spontaneously reoxidises to β-lap, thereby generating reactive oxygen species (ROS) and oxidative stress. To test for the consequences of an acute exposure of brain cells to β-lap, cultured primary rat astrocytes were incubated with β-lap for up to 4 h. The presence of β-lap in concentrations of up to 10 µM had no detectable adverse consequences, while higher concentrations of β-lap compromised the cell viability and the metabolism of astrocytes in a concentration- and time-dependent manner with half-maximal effects observed for around 15 µM β-lap after a 4 h incubation. Exposure of astrocytes to β-lap caused already within 5 min a severe increase in the cellular production of ROS as well as a rapid oxidation of glutathione (GSH) to glutathione disulfide (GSSG). The transient cellular accumulation of GSSG was followed by GSSG export. The β-lap-induced ROS production and GSSG accumulation were completely prevented in the presence of the NQO1 inhibitor dicoumarol. In addition, application of dicoumarol to β-lap-exposed astrocytes caused rapid regeneration of the normal high cellular GSH to GSSG ratio. These results demonstrate that application of β-lap to cultured astrocytes causes acute oxidative stress that depends on the activity of NQO1. The sequential application of β-lap and dicoumarol to rapidly induce and terminate oxidative stress, respectively, is a suitable experimental paradigm to study consequences of a defined period of acute oxidative stress in NQO1-expressing cells.Obesity is characterized by chronic inflammation of low grade. The cholinergic anti-inflammatory pathway favors the reduction of the inflammatory response. In this work the effect of stimulation of the cholinergic anti-inflammatory pathway on SHIRPA behavioral test and mitochondrial respiratory chain activity in obese mice was evaluated. The animals were paired in four groups saline + control diet; donepezil + control diet; saline + high-fat diet and donepezil + high-fat diet. 5 mg/kg/day orally of donepezil or saline were given 7 days before the beginning of the diet until completing 11 weeks of the experiment. Food intake and body weight were measured. At the end of the experiment the animals were submitted to the SHIRPA behavioral test, soon after they were killed by decapitation, the open abdominal cavity and the mesenteric fat were removed. The hypothalamus, hippocampus, prefrontal cortex, and striatum were removed for evaluation of the mitochondrial respiratory chain. It can be observed that donepezil prevented weight gain and food consumption, as well as a tendency to prevent the accumulation of mesenteric fat in obese animals. There was no behavioral change in obese animals, nor did the influence of donepezil on these parameters. On the other hand, donepezil did not prevent inhibition of complex I activity, prevented the inhibition of complex II, and showed a tendency to prevent IV complex activity inhibited in obesity. With these results it can be concluded that the activation of the cholinergic anti-inflammatory pathway is promising for the alterations found in obesity.Epilepsy is one of the most common diseases of the central nervous system. Recent studies have shown that a variety of inflammatory mediators play a key role in the pathogenesis of the disease. Ibuprofen (IBP) is a well-known anti-inflammatory agent that reduces the neuroinflammatory response and neuronal damage. In this study, we examined the effect of IBP in a rat model of pentylenetetrazol (PTZ)-induced chronic epilepsy. PTZ injection was given a total of 15 times on alternate days (over a period of 29 days) to induce epilepsy. The effects of IBP were evaluated by behavioral observation, EEG recording, Nissl staining, immunohistochemistry, Western blot analysis, and electrophysiological recording. The results showed that IBP alone affected the expression of cyclooxygenase-2 (COX-2) and neuronal excitability but did not cause epilepsy. IBP reduced seizure scores in the PTZ-treated rats, and it minimized the loss of hippocampal neurons. In addition, IBP decreased the secretion of COX-2, inhibited the activation of the NOD-like receptor 3 inflammasome, and reduced the secretion of the inflammatory cytokine interleukin-18. Furthermore, the results of whole-cell patch-clamp revealed that IBP affected action potential properties, including frequency, latency and duration in epileptic rats, suggesting that it may impact neuronal excitability. These effects of IBP may underlie its antiepileptic and neuroprotective actions.Addressing aggression in youth requires understanding of the range of social problem situations that may lead to biased social information processing (SIP). The present study investigated situation-specificity of SIP and analyzed whether SIP deficits and biases are found in ambiguous as well as clearly accidental situations in adolescents with clinical levels of externalizing behavior or with low intellectual level, congruent with mild intellectual disability. Adolescents (N = 220, Mage = 15.21) completed a SIP test on a mobile app with six videos with ambiguous, hostile, and accidental social problems. Caretakers, teachers, and adolescents themselves reported on youth externalizing behavior problems. In accidental situations specifically, adolescents with low IQ scores more often attributed purposeful intent to perpetrators than peers with borderline or average IQ scores. In accidental situations, adolescents with clinical levels of externalizing behavior generated and selected more aggressive responses than nonclinical adolescents, regardless of their cognitive level. In line with previous literature, the ambiguous situations also brought out SIP differences between IQ groups. These results suggest that not only ambiguous situations should be considered informative for understanding SIP biases, but situations in which adolescents are clearly accidentally disadvantaged bring out SIP biases as well, that may lead to conflicts with others.This article focuses on medical trials performed by Dr. Albert Kligman on the inmates of Philadelphia's Holmesburg Prison between 1951 and 1974, which have been widely criticized as exploitative. I seek to investigate the mechanics behind the "ethical blind spot" that enabled the American medical community to laud Kligman for his efforts while simultaneously condemning the medical atrocities of the Holocaust and supporting the development of the Nuremberg Code. I argue that this nonrecognition hinges on a colonial logic by which certain populations are produced as waste, both rhetorically and materially. Drawing on the incarcerated men's accounts included in Allen Hornblum's books on the subject, I trace the process by which human beings come to be reclassified as natural resources and their exploitation recast as industrious cultivation.
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