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Evidence of a geothermally active landscape is reported via an unusual biomarker distribution consistent with the presence of hydrothermal features seen today at Yellowstone National Park. The study of hydrothermalism in ancient settings and its impact on hominin evolution has not been addressed before, although the association of thermal springs in the proximity of archaeological sites documented here can also be found at other localities. The hydrothermal features and resources present at Olduvai Gorge may have allowed early hominins to thermally process edible plants and meat, supporting the possibility of a prefire stage of human evolution.

The dual-layer nitinol CASPER stent was designed to prevent plaque prolapse into its strut and periprocedural stroke.

To conduct a clinical trial for government approval of the device in patients at either high or normal risk for carotid endarterectomy (CEA).

Eligible patients had ≥50% symptomatic stenosis or ≥80% asymptomatic stenosis according to the North American Symptomatic Carotid Endarterectomy Trial methods (peak systolic velocity 130 and 230 cm/s on ultrasonography, respectively). The primary endpoint was the lack of major adverse events (MAEs), defined as death, stroke, and myocardial infarction within 30 days, and ipsilateral stroke within 1 year. The performance goal was set at 90.5%. MAE rates were also compared between the CEA high- and normal-risk groups.

140 carotid artery stenting procedures, including 40% of patients at high risk and 60% at normal risk for CEA, were performed in 13 institutes. MAEs occurred in two cases (one intraprocedural and one postprocedural stroke), and the MAE rate was 1.4%. The non-MAE rate was 98.6% according to Kaplan-Meier analysis, which was superior to the previously set performance goal. The deployment success, target lesion revascularization (TLR), in-stent restenosis, and cerebrovascular event rates were 99.3%, 2.4%, 8.5%, and 7.2%, respectively. The MAE rate in patients with normal CEA risk was 1.2%, which was similar to the high-risk CEA group, with no significant difference due to the small number of MAEs.

The MAE rate following use of the CASPER stent was low (1.4%). The MAE, deployment success, TLR, in-stenosis, and cerebrovascular event rates were similar to those of previous reports.

The MAE rate following use of the CASPER stent was low (1.4%). The MAE, deployment success, TLR, in-stenosis, and cerebrovascular event rates were similar to those of previous reports.

To examine the efficacy and safety of pegloticase in combination with methotrexate (MTX) in patients with uncontrolled gout in an exploratory, open-label clinical trial (ClinicalTrials.gov NCT03635957) prior to a randomized, controlled trial.

A multicenter, open-label efficacy and safety study of pegloticase with MTX co-treatment was conducted in patients with uncontrolled gout. Patients were administered oral MTX (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase treatment. The primary study outcome was the proportion of responders, defined as serum uric acid (sUA) < 6 mg/dL for ≥ 80% of the time during Month 6 (Weeks 20, 22, and 24). All analyses were performed on a modified intent-to-treat population, defined as patients who received ≥ 1 pegloticase infusion.

Seventeen patients were screened and 14 patients (all men, average age 49.3 ± 8.7 years) were enrolled. On Day 1, mean sUA was 9.2 ± 2.5 mg/dL, and 12 of the 14 patients had visible tophi. At the 6-month timepoint, 11/14 (78.6%, 95% CI 49.2-95.3%) met the responder definition, with 3 patients discontinuing after meeting protocol-defined treatment discontinuation rules (preinfusion sUA values > 6 mg/ dL at 2 consecutive scheduled visits). All patients tolerated MTX. No new safety concerns were identified.

In this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with MTX and pegloticase as compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of MTX or placebo with pegloticase to validate these open-label findings.

In this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with MTX and pegloticase as compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of MTX or placebo with pegloticase to validate these open-label findings.

To define the association between oral and systemic manifestations of Sjӧgren's syndrome (SS) and quality of life.

We analyzed a cross-sectional survey conducted by the Sjӧgren's Foundation in 2016, with 2961 eligible responses. We defined oral symptom and sign exposures as parotid gland swelling, dry mouth, mouth ulcers/sores, oral candidiasis, trouble speaking, choking or dysphagia, sialolithiasis or gland infection, and dental caries. Systemic exposures included interstitial lung disease, purpura/petechiae/cryoglobulinemia, vasculitis, neuropathy, leukopenia, interstitial nephritis, renal tubular acidosis, autoimmune hepatitis, primary biliary cholangitis, or lymphoma. Outcomes included SS-specific quality of life questions generated by SS experts and patients.

Using multivariable regression models adjusted for age, sex, race, and employment, we observed that mouth ulcers or sores, trouble speaking, and dysphagia were associated with poor quality of life. The following oral aspects had the greatest impact on these following quality of life areas i) mouth ulcers/sores on the challenge and burden of living with SS (odds ratio [OR] 4.26, 95% confidence interval [CI] 2.89- 5.48), ii) trouble speaking on memory and concentration (OR 4.24, 95% CI 3.28-5.48), and iii) dysphagia on functional interference (OR 4.25, 95% CI 3.13-5.79). L-glutamate mouse In contrast, systemic manifestations were associated with quality of life to a lesser extent or not at all.

Oral manifestations of SS, particularly mouth ulcers or sores, trouble speaking, and dysphagia, were strongly associated with worse quality of life. Further study and targeted treatment of these oral manifestations provides the opportunity to improve quality of life in patients with SS.

Oral manifestations of SS, particularly mouth ulcers or sores, trouble speaking, and dysphagia, were strongly associated with worse quality of life. Further study and targeted treatment of these oral manifestations provides the opportunity to improve quality of life in patients with SS.

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