Meningoencephalomyelitis and pneumonia caused by Cryptococcus spp. in a cat - case report

ABSTRACT Cryptococcosis is an important systemic mycosis with worldwide distribution that affects men and also domestic and wild animals. The infection is acquired by inhalation of the fungus or basidiospores present in the environment and may manifest as localized nasal or ocular injury, pulmonary illness or, less commonly, as meningoencephalomyelitis. Long-term treatment is necessary, and the prognosis is reserved. This paper aims to report a case of invasive cryptococcosis in a domestic cat that was presented with neurological signs. It is intended to emphasize the systemic nature of the infection and its possible routes of infection, reinforcing the importance of investigating this disease as a differential diagnosis of clinical manifestations with neurological involvement in cats

Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

Gene-regulatory network analysis is a powerful approach to elucidate the molecular processes and pathways underlying complex disease. Here we employ systems genetics approaches to characterize the genetic regulation of pathophysiological pathways in human temporal lobe epilepsy (TLE). Using surgically acquired hippocampi from 129 TLE patients, we identify a gene-regulatory network genetically associated with epilepsy that contains a specialized, highly expressed transcriptional module encoding proconvulsive cytokines and Toll-like receptor signalling genes. RNA sequencing analysis in a mouse model of TLE using 100 epileptic and 100 control hippocampi shows the proconvulsive module is preserved across-species, specific to the epileptic hippocampus and upregulated in chronic epilepsy. In the TLE patients, we map the trans-acting genetic control of this proconvulsive module to Sestrin 3 (SESN3), and demonstrate that SESN3 positively regulates the module in macrophages, microglia and neurons. Morpholino-mediated Sesn3 knockdown in zebrafish confirms the regulation of the transcriptional module, and attenuates chemically induced behavioural seizures in vivo

Downregulation of drug transport and metabolism in mice bearing extra-hepatic malignancies

There is increasing evidence of a systemic inflammatory response associated with malignancy, which may have an impact on both drug disposition and resistance to cytotoxic therapy. The impact of inflammation on drug disposition was studied in mice bearing a number of common tumour xenografts. C57BL/6 mice were inoculated with tumour xenografts. Hepatic expressions of Cyp3a and drug transporters were analysed at the mRNA, protein and functional levels (Cyp3a only). Circulating serum cytokines and the hepatic expression of acute phase proteins (APPs) were measured. Intratumoral levels of multidrug resistance genes were determined. Tumour xenografts elicited an inflammatory response that coincided with repression in hepatic Cyp3a11 activity and the expression of a number of hepatic drug transporters. With tumour growth, a progressive reduction in hepatic Cyp3a11 mRNA expression was seen. Conversely, an increase in the hepatic APP expression and circulating interleukin (IL)-6 levels was observed. Furthermore, a correlation was seen between increased intratumoral expression of the multidrug resistance gene, Mdr1a, and levels of circulating IL-6. Malignancy results in reduced hepatic drug disposition that correlates with an associated inflammatory response. Reduction of inflammation may improve the clinical outcome for patients receiving chemotherapeutic agents that undergo hepatic metabolism

The presence of a systemic inflammatory response predicts poorer survival in patients receiving adjuvant 5-FU chemotherapy following potentially curative resection for colorectal cancer

There is increasing evidence that the presence of a systemic inflammatory response plays an important role in survival following curative resection for colorectal cancer. The present study evaluated the relationship between C-reactive protein concentrations and survival in a cohort of patients receiving adjuvant 5-fluorouracil (5-FU) chemotherapy following potentially curative resection for colorectal cancer. In all, 222 patients undergoing potentially curative resection for colorectal cancer were studied. Of these, 50 patients received adjuvant 5-FU-based chemotherapy. Circulating concentrations of C-reactive protein were measured prior to surgery. The minimum follow-up was 15 months; the median follow-up of the survivors was 38 months. During this period 61 patients died, 32 patients of their cancer and 29 of intercurrent disease. In those patients who did not receive adjuvant chemotherapy, age (P<0.001), Dukes stage (P<0.05) and an elevated C-reactive protein (P<0.01) were significantly associated with survival. In those patients who did receive adjuvant chemotherapy, an elevated C-reactive protein concentration (P<0.01) was significantly associated with survival. The presence of a systemic inflammatory response is an independent predictor of poor outcome in patients receiving adjuvant 5-FU-based chemotherapy following potentially curative resection for colorectal cancer

Pollination and dispersal trait spectra recover faster than the growth form spectrum during spontaneous succession in sandy old‐fields

Question: Spontaneous succession is the most natural and cost‐effective solution for grassland restoration. However, little is known about the time required for the recovery of grassland functionality, i.e., for the recovery of reproductive and vegetative processes typical of pristine grasslands. Since these processes operate at different scales, we addressed the question: do reproductive and vegetative processes require different recovery times during spontaneous succession? Location: Kiskunság sand region (Central Hungary). Methods: As combinations of plant traits can be used to highlight general patterns in ecological processes, we compared reproductive (pollination‐ and dispersal‐related) and vegetative (growth form) traits between recovered grasslands of different age (&lt;10 years old; 10–20 years old; 20–40 years old) and pristine grasslands. Results: During spontaneous succession, the reproductive trait spectra became similar to those of pristine grasslands earlier than the vegetative ones. In arable land abandoned for 10 years, pollination‐ and dispersal‐related trait spectra did not show significant difference to those of pristine grasslands; anemophily and anemochory were the prevailing strategies. Contrarily, significant differences in the growth form spectrum could be observed even after 40 years of abandonment; in recovered grasslands erect leafy species prevailed, while the fraction of dwarf shrubs and tussock‐forming species was significantly lower than in pristine grasslands. Conclusions: The recovery of the ecological processes of pristine grasslands might require different amounts of time, depending on the spatial scale at which they operate. The reproductive trait spectra recovered earlier than the vegetative one, since reproductive attributes first determine plant species sorting at the regional level towards their respective habitats. The recovery of the vegetative trait spectrum needs more time as vegetative‐based interactions operate on a smaller spatial scale. Thus, vegetative traits might be more effective in the long‐term assessment of restoration success than the reproductive ones

Clinical pharmacology of cancer therapies in older adults

This abbreviated review outlines the physiologic changes associated with aging, and examines how these changes may affect the pharmacokinetics and pharmacodynamics of anticancer therapies. We also provide an overview of studies that have been conducted evaluating the pharmacology of anticancer therapies in older adults, and issue a call for further research

Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

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