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Silver Wyatt posted an update 6 months, 2 weeks ago
names are presented accurately and in the correct sequence (given name, middle name/initial, family name). VX-478 Author 1 Given name Last name . Author 2 Given name Last name . Author 3 Given name Last name . Author 4 Given name Last name . Also, kindly confirm the details in the metadata are correct.ok.In the summers of 2019 and 2020, a previously undescribed disease occurred in both juvenile and adult shellfish, causing mass mortalities in cultured pearl production, characterized by the major symptom of extreme atrophy of the soft tissues, including the mantle. However, the causative organism was uncertain. We isolated Vibrio sp. strain MA3 from the mantles of diseased pearl oysters Pinctada fucata. Analyses of 16S rRNA gene and DNA gyrase sequence homologies and its biochemical and morphological characteristics suggested that strain MA3 is a new strain of Vibrio alginolyticus. In addition, a hemolysin gene (Vhe1) of strain MA3 was detected as one of the virulence factors, and the complete sequence was determined. BLAST searches showed that Vhe1 shares 99.8% nucleotide sequence identity with Vibrio alginolyticus strain A056 lecithin-dependent hemolysin (ldh) gene, complete cds. Experimental infection of healthy oysters via injection with strain MA3 indicated it could cause high mortalities of the typically affected oysters from which the strain was isolated. These results suggest that the newly isolated Vibrio sp. strain MA3 is a putative causal agent of the recent disease outbreaks in Akoya pearl oysters.
Little is known about how adverse, midlife metabolic profiles impact future physical functioning. We hypothesized that a higher number of midlife metabolic syndrome (MetS) components are associated with poorer physical performance in early old age for multi-ethnic women.
MetS status from 1996-2011 (8 visits) and objective physical performance in 2015/2016 (short physical performance battery (SPPB; 0-12), 40-foot walk (m/s), 4-meter gait speed (m/s), chair stands (sec), stair climb (sec)) were assessed in the Study of Women’s Health Across the Nation (SWAN; n=1722; age 65.4±2.7 years; 26.9% African American, 10.1% Chinese, 9.8% Japanese, 5.5% Hispanic). Poisson latent class growth modeling identified MetS component trajectory groups none (23.9%), 1=low-MetS (28.7%), 2=mid-MetS (30.9%), and >3=high-MetS (16.5%). Adjusted linear regression related MetS groups to physical performance outcomes.
High-MetS versus none had higher BMI, pain, financial strain, and lower physical activity and self-reported health (p<0.0001). Compared to White, African American and Hispanic women were more likely to be in the high-MetS groups and had worse physical functioning along with Chinese women (SPPB, chair stand, stair climb, and gait speed – not Hispanic). After adjustments, high-MetS versus none demonstrated significantly worse 40-ft walk (β-0.08; 95% CI-0.13, -0.03), gait speed (β-0.09; 95% CI-0.15, -0.02), SPPB (β-0.79; 95% CI -1.15, -0.44), and chair stands (β0.69; 95% CI 0.09, 1.28), but no difference in stair climb.
Midlife MetS groups were related to poor physical performance in early old age multi-ethnic women. Midlife management of metabolic function may improve physical performance later in life.
Midlife MetS groups were related to poor physical performance in early old age multi-ethnic women. Midlife management of metabolic function may improve physical performance later in life.
Brain metastases (BM) are a frequent complication of malignant melanoma (MM), with limited treatment options and poor survival. Prevention of BM could be more effective and better tolerated than treating established BM in various conditions.
To investigate the temporo-spatial dynamics of PI3K/Akt/mTOR (PAM) pathway activation during BM formation and the preventive potential of its inhibition, in vivo molecular imaging with an Akt biosensor was performed, and long-term intravital multiphoton microscopy through a chronic cranial window in mice.
In vivo molecular imaging revealed invariable PAM pathway activation during the earliest steps of brain colonization. In order to perform a long-term intravascular arrest and to extravasate, circulating MM cells needed to activate their PAM pathway during this process. However, the PAM pathway was quite heterogeneously activated in established human brain metastases, and its inhibition with the brain-penetrant PAM inhibitor GNE-317 resulted in only modest therapeutic effects in mice. In contrast, giving GNE-317 in preventive schedules that included very low doses effectively reduced growth rate and number of BM in two MM mouse models over time, and led to an overall survival benefit. Longitudinal intravital multiphoton microscopy found that the first, rate-limiting steps of BM formation – permanent intravascular arrest, extravasation, and initial perivascular growth – are most vulnerable to dual PI3K/mTOR inhibition.
These findings establish a key role of PAM pathway activation for critical steps of early metastatic brain colonization and reveal its pharmacological inhibition as a potent avenue to prevent the formation of clinically relevant BM.
These findings establish a key role of PAM pathway activation for critical steps of early metastatic brain colonization and reveal its pharmacological inhibition as a potent avenue to prevent the formation of clinically relevant BM.
Chronic kidney disease (CKD) and diabetes are associated with dyslipidaemia, metabolic abnormalities, and atherosclerotic risk. Nuclear magnetic resonance (NMR) spectroscopy provides much more detail on lipoproteins than traditional assays.
In about 38,000 participants from the Mexico City Prospective Study, aged 35-84 years and not using lipid-lowering medication, NMR spectroscopy quantified plasma concentrations of lipoprotein particles, their lipidic compositions, and other metabolic measures. Linear regression related low eGFR (<60mL/min/1.73m2) to each NMR-measure after adjustment for confounders and for multiplicity. Analyses were done separately for those with and without diabetes.
Among the 38,081 participants (mean age 52 years, 64% women), low eGFR was present for 4.8% (306/6,403) of those with diabetes and 1.2% (365/31,678) of those without diabetes. Among both those with and without diabetes, low eGFR was significantly associated with higher levels of 58 NMR-measures – including apolipoprotein B (Apo-B), the particle numbers of most Apo-B containing lipoproteins, the cholesterol and triglycerides carried in these lipoproteins, several fatty acids, total cholines and phosphatidylcholine, citrate, glutamine, phenylalanine, β-OH-butyrate, and the inflammatory measure glycoprotein-A – and significantly lower levels of 13 NMR-measures, including medium and small high-density lipoprotein particle measures, very low-density lipoprotein particle size, the ratio of saturatedtotal fatty acids, valine, tyrosine, and aceto-acetate.
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