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A cluster of cases of pneumonia of unknown etiology emerged in Wuhan, China, at the end of December 2019. The cluster was largely associated with a seafood and animal market. A novel Betacoronavirus was quickly identified as the causative agent, and it is shown to be related genetically to SARS-CoV and other bat-borne SARS-related Betacoronaviruses. The number of cases increased rapidly and spread to other provinces in China, as well as to another 4 countries. To help control the spread of the virus, a “cordon sanitaire” was instituted for Wuhan on January 23, 2020, and subsequently extended to other cities in Hubei Province, and the outbreak declared a Public Health Emergency of International Concern by the Director General of the World Health Organization on January 30, 2020. The virus was named SARS-CoV-2 by the International Committee for the Taxonomy of Viruses, and the disease it causes was named COVID-19 by the World Health Organization. This article described the evolution of the outbreak, and the known properties of the novel virus, SARS-CoV-2 and the clinical disease it causes, and the major public health measures being used to help control it’s spread. These measures include social distancing, intensive surveillance and quarantining of cases, contact tracing and isolation, cancellation of mass gatherings, and community containment. The virus is the third zoonotic coronavirus, after SARS-CoV and MERS-CoV, but appears to be the only one with pandemic potential. However, a number of important properties of the virus are still not well understood, and there is an urgent need to learn more about its transmission dynamics, its spectrum of clinical severity, its wildlife origin, and its genetic stability. In addition, more research is needed on possible interventions, particularly therapeutic and vaccines.Six articles in the June 2020 issue of the American Journal of Psychiatry address the overall construct of cognition. These articles have a broad connection to cognition, which is itself a broad concept. From the experimental psychology perspective, cognition is the set of processes associated with attending, learning, knowing, and remembering. From the clinical perspective, a number of neuropsychiatric conditions are defined by the presence of cognitive impairment, with onset ranging from childhood, such as attention deficit hyperactivity disorder and intellectual disability, to later life, such as dementia. Other conditions have notable cognitive impairments even if specific cognitive impairments are not an explicit part of their formal diagnostic criteria, including autism spectrum disorder and schizophrenia. Thus, the array of articles in this issue are related to each other and also may make important points about the role of cognition in everyday functioning and the connections between cognitive impairments in neuropsychiatric conditions and in the human population in general. Further, these articles address the neurobiological substrates that have an impact on cognition, with important implications in other domains, such as genomics. Finally, through sophisticated research methods, they clarify the results of previous studies that were affected by a variety of methodological challenges.Maintaining water homeostasis is fundamental for cellular function. Many diseases and drugs affect water balance and plasma osmolality. Water homeostasis studies in small animals require the use of invasive or terminal methods that make intracellular and extracellular fluid volume (ICF and ECF) monitoring over time stressful and time consuming. We examined the feasibility of monitoring mice ECF by a non-invasive method, using time-domain nuclear magnetic resonance (TD-NMR). This technique allows differentiating protons in a liquid environment (free fluid) from protons in soft tissues containing a majority of either small molecules (lean) or large molecules (fat). Moreover, this apparatus enables rapid, non-invasive, and repeated measurements on the same animal. We assessed the feasibility of coupling TD-NMR analysis to a longitudinal metabolic cage study by monitoring mice daily. We determined the effect of a 24-hour water deprivation on mice body parameters and detected a sequential and overlapping decrease in free fluid and lean mass during water deprivation. Finally, we studied the effect of mineralocorticoids that are known to induce a transient increase in the ECF but for which no direct measurements have been performed in mice. We showed for the first time that mineralocorticoids induce a transient ~15% increase in free fluid in conscious mice. TD-NMR is therefore the first method to allow direct measurement of discrete changes in the ECF in conscious small animals. This method allows analysis of kinetic changes to stimuli prior to investigating with terminal methods and will allow further understanding of fluid disorders.Long non-coding RNA NEAT1 was reported to promote liver fibrosis progression. However, its molecular mechanism in renal fibrosis is not elucidated. In this study, in vitro model of renal fibrosis was established with HK-2 and HKC-8 cells treated by TGF-β1. C57BL/6 mice were used to induce the in vivo model with unilateral ureteral obstruction (UUO). Our results indicated NEAT1 and collagen I levels were significantly up-regulated while miR-129 was obviously down-regulated in the progression of renal fibrosis. Meanwhile, NEAT1 knocking down or miR-129 overexpression inhibited collagen I deposition, EMT process and inflammation response to suppress the renal fibrosis. NEAT1 directly targeted miR-129, and miR-129 directly bound to collagen I. Downregulation of miR-129 reversed inhibition of renal fibrosis induced by NEAT1 silencing, and upregulation collagen I also reversed inhibition of renal fibrosis caused by miR-129 overexpression. NEAT1 knocking down alleviated renal fibrosis in UUO mice. In conclusion, NEAT1 sponged miR-129 to modulate EMT process and inflammation response of renal fibrosis by regulation of collagen I. Our study indicated a novel role in the regulation of renal fibrosis and provided a new potential treatment target for renal fibrosis.Background A system for sorbent assisted peritoneal dialysis (SAPD) was designed to continuously recirculate dialysate via a tidal mode using a single lumen peritoneal catheter with regeneration of spent dialysate by means of sorbent technology. We hypothesize that SAPD treatment will maintain a high plasma-to-dialysate concentration gradient and increase the mass transfer area coefficient of solutes. Thereby, the SAPD system may enhance clearance while reducing the number of exchanges. Application is envisaged at night as a bedside device (12 kg, nighttime system). A wearable system (2.0 kg, daytime system) may further enhance clearance during the day. Methods Urea, creatinine and phosphate removal was studied with the day- and nighttime system (n=3 per system) by recirculating 2 L of spent peritoneal dialysate via a tidal mode (mean flow rate 50 and 100 ml/min, respectively) for 8 h. Time-averaged plasma clearance over 24 h was modeled assuming one 2-L exchange per day, an increase in MTAC and 0.9 L ultrafiltration per day. Results Urea, creatinine and phosphate removal was 33.2±4.1 mmol, 5.3±0.5 mmol, and 6.2±1.8 mmol, respectively, with the daytime system, and 204±28 mmol, 10.3±2.4 mmol and 11.4±2.1 mmol, respectively, with the nighttime system. Time-averaged plasma clearances of urea, creatinine and phosphate were 9.6±1.1 mL/min, 9.6±1.7 mL/min and 7.0±0.9 mL/min, respectively, with the nighttime system and 10.8±1.1 mL/min, 13.4±1.8 mL/min, 9.7±1.6 mL/min, respectively, with the day- and nighttime system. Conclusions SAPD treatment may improve removal of uremic toxins compared with conventional PD, provided that peritoneal mass transport will increase.Acutely increased renal venous pressure (RVP) impairs renal function, but the long-term impact is unknown. We investigated whether chronic RVP elevation impairs baseline renal function and prevents exacerbation of renal dysfunction and cardiovascular instability upon further RVP increase. RVP elevation (20-25 mmHg) or sham operation (sham) was performed in rats. After 1 wk (n = 17) or 3 wk (n = 22), blood pressure, RVP, renal blood flow (RBF), renal vascular conductance (RVC), and glomerular filtration rate (GFR) were measured at baseline and during superimposed RVP increase. Chronic RVP elevation induced extensive renal venous collateral formation. RVP fell to 6 ± 1 mmHg at 1 wk and 3 ± 1 mmHg at 3 wk. Baseline blood pressure and heart rate were unaltered compared with sham. RBF, RVC, and GFR were reduced at 1 wk but normalized by 3 wk. Upon further RVP increase, the drop in mean arterial pressure was attenuated at 3 wk compared with 1 wk (P less then 0.05), whereas heart rate fell comparably across all groups; the mean arterial pressure-heart rate relationship was disrupted at 1 and 3 wk. RBF fell to a similar degree as sham at 1 wk (-2.3 ± 0.7 vs. -3.9 ± 1.2 mL/min, P = 0.066); however, at 3 wk, this was attenuated compared with sham (-1.5 ± 0.5 vs. -4.2 ± 0.7 mL/min, P less then 0.05). The drop in RVC and GFR was attenuated at 1 and 3 wk (P less then 0.05). Thus, chronic RVP elevation induced by partial renal vein ligation elicits extensive renal venous collateral formation, and although baseline renal function is impaired, chronic RVP elevation in this manner induces protective adaptations in kidneys of healthy rats, which attenuates the hemodynamic response to further RVP increase.Loss of muscle proteins increases the morbidity and mortality of patients with chronic kidney disease (CKD) and there are no reliable preventive treatments. We uncovered a STAT3, CEBPδ to myostatin signaling pathway that activates muscle protein degradation in mice with CKD or cancer; we also identified a small molecule inhibitor of STAT3 (TTI-101) that blocks this pathway. To evaluate TTI-101 as a treatment of CKD-induced cachexia, we measured TTI-101 pharmacokinetics (PK) and pharmacodynamics (PD) in control and CKD rats that were orally administrated TTI-101or its diluent. Two groups of gavage-fed rats, sham-operated, control rats and CKD rats were studied. Plasma was collected serially (0, 0.25, 0.5, 1, 2, 4, 8 and 24 hr.) following TTI-101 administration (at oral doses of 0, 10, 30, or 100 mg/kg). Plasma levels of TTI-101 were measured by LC-MS/MS and PK results analyzed with the PKsolver program. Plasma TTI-101 levels increased linearly with doses; the maximum plasma concentrations (Cmax) and time to maximal (Tmax) plasma levels (~1 hour) were similar in sham-operated, control and CKD rats. Notably, gavage treatment of TTI-101 for 3 days produced TTI-101 muscle levels in sham-control and CKD rats that were not significantly different. CKD rats that received TTI-101 for 7 days had suppression of activated STAT3 and improved muscle grip strength; there also was a trend for increasing body and muscle weights. TTI-101 was tolerated at doses of 100 mg/kg/day for 7 days. These results with TTI-101 in rats warrants its development as a treatment of cachexia in humans.Hydroxysteroid sulfotransferase 2B1b (SULT2B1b) plays a critical role in hepatic energy homeostasis. read more Liver X receptors (LXRs) are implicated in multiple physiological functions, including the inhibition of hepatocyte proliferation and regulation of fatty acid and cholesterol metabolism. We have previously reported that SULT2B1b promotes hepatocyte proliferation by inactivating LXR signaling in vivo and in vitro, leading to our hypothesis that SULT2B1b promotes fatty liver regeneration. In the present study, female C57BL/6 and S129 mice were fed a high-fat diet for 8 weeks to establish a nonalcoholic fatty liver disease (NAFLD) mouse model. 70% partial hepatectomy (PH) was performed to induce liver regeneration. Our experiments revealed that the SULT2B1b overexpression significantly promotes the regeneration of hepatocytes in NAFLD C57BL/6 mice after PH, increasing liver regrowth by 11% within 1 day, and then by 21%, 33%, and 24% by 2, 3, and 5 days post-PH, respectively. Compared with the wild-type NAFLD S129 mice, SULT2B1 deletion NAFLD S129 mice presented reduced hepatocyte regeneration at postoperative day 2, as verified by decreased liver regrowth (37.