Notes

ATI-2307 Exhibits Equivalent Antifungal Task in Cryptococcus neoformans Specialized medical Isolates With High and Low Fluconazole IC50.
Outdoor air pollution has been linked to poor sleep health, but limited studies have investigated the relationship between solid cooking fuels and sleep health in adults. Therefore, we analyzed data from the China Health and Retirement Survey (CHARLS), a national survey of about 17,000 residents aged over 45. Participants were restricted to those who participated in CHARLS 2011, 2013 and 2015 (n = 8,668). Sleep health was indicated by self-reported average sleep hours at night and the numbers of unrested days/week in CHARLS 2015. We analyzed cooking fuel types reported and assessed the duration of solid fuels usage as consistent (indicated use in all three surveys or 6 + years) or inconsistent use (indicated use in one or two surveys or 1-4 years). We found consistent use of solid fuels was associated with a shorter sleep duration (OR = 1.17 95% CI 1.01, 1.35 for ≤ 6 h vs. 7-9 h/day) and higher frequencies of feeling unrested (OR = 1.32 95% CI 1.12, 1.55 for ≥ 5 days/week vs. none) compared with cleaner fuels use. The associations for inconsistent solid fuels use and sleep health were in the similar direction but smaller in magnitude. Further research is needed to confirm our findings and evaluate the exposure impact of specific fuel types to inform intervention strategies.The prevalence of clinically defined problematic substance use among stroke patients is overlooked and its association with post-stroke depression (PSD) is unknown. Our aims were to (1) estimate the proportion of stroke patients with a problematic substance use as defined by clinical screening scales; (2) determine the proportion of PSD at three months of follow-up; (3) explore if the baseline severity in substance use and its evolution are independent predictors of PSD. A cohort of first-ever non-severe stroke adult patients was screened at baseline and three months post-stroke using recommended cut-off scores of standardized scales for tobacco, alcohol and cannabis abuse. PSD was defined using the Center of Epidemiological Studies Depression scale score. Out of the 244 eligible patients, 74 (30.3%) presented a problematic substance use, including 21 (8.6%) polydrug abusers. Among these patients, the prevalence of PSD was 50.8%, including 29.5% of severe depression. The severity of tobacco dependence at baseline was found to double the risk (OR 1.59, 95% CI 1.05-2.43) of presenting a PSD, independently of previously reported risk factors. We found no significant evidence for an effect of the evolution in substance use at follow-up. Addictive disorders are part of the critical unmet needs that should be addressed in the management of PSD.Gastrointestinal (GI) strictures are difficult to treat in a variety of disease processes. Currently, there are no Food and Drug Administration (FDA) approved drugs for fibrosis in the GI tract. One of the limitations to developing anti-fibrotic drugs has been the lack of a reproducible, relatively inexpensive, large animal model of fibrosis-driven luminal stricture. This study aimed to evaluate the feasibility of creating a model of luminal GI tract strictures. Argon plasma coagulation (APC) was applied circumferentially in porcine esophagi in vivo. Follow-up endoscopy (EGD) was performed at day 14 after the APC procedure. We noted high grade, benign esophageal strictures (n = 8). read more All 8 strictures resembled luminal GI fibrotic strictures in humans. These strictures were characterized, and then successfully dilated. A repeat EGD was performed at day 28 after the APC procedure and found evidence of recurrent, high grade, fibrotic, strictures at all 8 locations in all pigs. Pigs were sacrificed and gross and histologic analyses performed. Histologic examination showed extensive fibrosis, with significant collagen deposition in the lamina propria and submucosa, as well as extensive inflammatory infiltrates within the strictures. In conclusion, we report a porcine model of luminal GI fibrotic stricture that has the potential to assist with developing novel anti-fibrotic therapies as well as endoscopic techniques to address recurring fibrotic strictures in humans.Multi-tracer imaging can provide useful information in the definitive diagnosis and research of medical, biological, and pharmaceutical sciences. Single-photon emission computed tomography (SPECT) is one of the nuclear medicine imaging modalities widely used for diagnosis or medical research and has a multi-tracer imaging capability. One of the drawbacks of multi-tracer imaging is crosstalk from other gamma rays, which affects the reconstructed image. Scattering correction methods, such as the dual- and triple-energy window methods, are used for conventional SPECT imaging to reduce the background caused by the crosstalk. This study proposes another crosstalk reduction method. Some nuclides emit two or more gamma rays through intermediate levels. Thus, detecting these gamma rays with the coincidence method allows us to distinguish a true gamma ray signal and a background signal. The nuclide position can be estimated at the intersection of two gamma rays using collimators. We demonstrate herein simultaneous 111In and 177Lu imaging via the double-photon coincidence method using GAGG detectors and parallel hole collimators. The double-photon coincidence method greatly reduces the background caused by other gamma rays and offers higher-quality images than does conventional imaging.In this study, we show that the discharge voltage pattern of a supercapacitor exhibiting fractional-order behavior from the same initial steady-state voltage into a constant resistor is dependent on the past charging voltage profile. The charging voltage was designed to follow a power-law function, i.e. [Formula see text], in which [Formula see text] (charging time duration between zero voltage to the terminal voltage [Formula see text]) and p ([Formula see text]) act as two variable parameters. We used this history-dependence of the dynamic behavior of the device to uniquely retrieve information pre-coded in the charging waveform pattern. Furthermore, we provide an analytical model based on fractional calculus that explains phenomenologically the information storage mechanism. The use of this intrinsic material memory effect may lead to new types of methods for information storage and retrieval.Endocapillary proliferation occurs in various types of glomerulonephritis (GN), with varying prognoses. We examined 42 renal biopsy samples representing endocapillary proliferative lesions from post-streptococcal acute GN (PSAGN), Henoch-Schönlein purpura nephritis (HSPN), and lupus nephritis (LN). In PSAGN, the glomerular capillary network was maintained, although severe lesions displayed dots or short, curved lines, indicating CD34-positive capillaries and suggesting capillary obstruction. Conversely, patients with LN and HSPN displayed obstruction of CD34-positive capillaries with dissociation from the glomerular basement membrane even in mild lesions. According to computer-assisted morphologic analysis, the cell density did not differ between the diseases. However, in PSAGN, the number of capillary loops was significantly increased, with a larger glomerular capillary luminal area than in the other groups. In addition, the number and frequency of CD163-positive cells (M2 macrophages) tended to be higher in PSAGN, while there were no significant differences in the number of CD68-positive (total) macrophages. These results indicate that in PSAGN, endothelial cell damage is less severe, and angiogenesis may be promoted. The severity of endothelial cell injury in each disease may be associated with differences in infiltrating inflammatory cell phenotypes.Stress can impact perception, especially during use-of-force. Research efforts can thus advance both theory and practice by examining how perception during use-of-force might drive behavior. The current study explored the relationship between perceptual judgments and performance during novel close-combat training. Analyses included perceptual judgments from close-combat assessments conducted pre-training and post-training that required realistic use-of-force decisions in addition to an artificially construed stress-inoculation event used as a training exercise. Participants demonstrated significant reductions in situational awareness while under direct fire, which correlated to increased physiological stress. The initial likelihood of firing upon an unarmed person predicted the perceptual shortcomings of later stress-inoculation training. Subsequently, likelihood of firing upon an unarmed person was reduced following the stress-inoculation training. These preliminary findings have several implications for low or zero-cost solutions that might help trainers identify individuals who are underprepared for field responsibilities.Matrix metalloproteinase13 (MMP13) can be released by keratinocytes and fibroblasts and involved in the pathogenesis of skin disorders. Retinoic acid derivative drugs include tazarotene and acitretin. Tazarotene/acitretin and narrow-band ultraviolet B (NB-UVB) irradiation are common treatment options for psoriasis. However, their impact on MMP13 expression in the context of psoriasis has yet to be determined. The expression of MMP13 was analyzed in patients with psoriasis. The effects of tazarotene/acitretin and NB-UVB on MMP13 expression were also investigated in a mouse model of psoriasis. Human HaCaT keratinocytes were exposed to acitretin or NB-UVB and then assayed for cell proliferation and MMP13 expression levels. We showed that patients with psoriasis had increased levels of MMP13 protein in skin lesions and serum samples. Exposure to acitretin and NB-UVB irradiation alone or in combination led to reduction of cell proliferation and MMP13 expression in HaCaT cells. Consistently, tazarotene treatment or NB-UVB irradiation attenuated imiquimod-induced psoriasis-like dermatitis and decreased MMP13 expression in a mouse model. Based on these from HaCaT keratinocytes cells and animal experiments, we suggest that tazarotene/acitretin and NB-UVB irradiation can inhibit the expression of MMP13 in HaCaT keratinocytes and psoriasis mouse models. Blockade of MMP13 activity may have therapeutic potential in improving symptoms of psoriasis.All medically important unicellular protozoans cannot synthesize purines de novo and they entirely rely on the purine salvage pathway (PSP) for their nucleotide generation. Therefore, purine derivatives have been considered as a promising source of anti-parasitic compounds since they can act as inhibitors of the PSP enzymes or as toxic products upon their activation inside of the cell. Here, we characterized a Trypanosoma brucei enzyme involved in the salvage of adenine, the adenine phosphoribosyl transferase (APRT). We showed that its two isoforms (APRT1 and APRT2) localize partly in the cytosol and partly in the glycosomes of the bloodstream form (BSF) of the parasite. RNAi silencing of both APRT enzymes showed no major effect on the growth of BSF parasites unless grown in artificial medium with adenine as sole purine source. To add into the portfolio of inhibitors for various PSP enzymes, we designed three types of acyclic nucleotide analogs as potential APRT inhibitors. Out of fifteen inhibitors, four compounds inhibited the activity of the recombinant APRT1 with Ki in single µM values.
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