Correspondences - Online Journal For The Academic Study of Western Esotericism, Volume 2.2

Welcome to Correspondences, an international, peer-reviewed online journal devoted to the academic study of Western esotericism. By providing a wider forum of debate regarding issues and currents in Western esotericism than has previously been possible, Correspondences is committed to publishing work of a high academic standard as determined by a peer-review process, but does not require academic credentials as prerequisite for publication. Students and non-affiliated academics are encouraged to join established scholars in submitting insightful, well-researched articles that offer new ideas, positions, or information to the field

Pulmonary hypertension associated with COPD

Although the prevalence of pulmonary hypertension (PH) in individuals with chronic obstructive pulmonary disease (COPD) is not known precisely, approximately 10%–30% of patients with moderate to severe COPD have elevated pulmonary pressures. The vast majority of PH associated with COPD is mild to moderate and severe PH occurs in <5% of patients. When COPD is associated with PH, both mortality and morbidity are increased. There are no clinical or physical examination findings that accurately identify patients with underlying PH. Radiographic imaging findings are specific but not sensitive indicators of PH. Echocardiography is the principle noninvasive diagnostic test but may be technically limited in a significant proportion of patients with COPD. Right heart catheterization is required for accurate measurement of pulmonary pressures. The combined effects of inflammation, endothelial cell dysfunction, and angiogenesis appear to contribute to the development of PH associated with COPD. Systemic vasodilators have not been found to be effective therapy. Selective pulmonary vasodilators including inhaled nitric oxide and phosphodiesterase inhibitors are promising treatments for patients with COPD associated PH but further evaluation of these medications is needed prior to their routine use

Baseline features and reasons for nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) study, a colorectal cancer screening trial

IMPORTANCE: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. OBJECTIVE: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference\u27s association with geographic and temporal factors. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. EXPOSURE: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. MAIN OUTCOMES AND MEASURES: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. RESULTS: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P \u3c .001) or other screening tests (46 [1.0%] P \u3c .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). CONCLUSIONS AND RELEVANCE: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences

Correspondences - Online Journal For The Academic Study of Western Esotericism, Volume 6(2)

Welcome to Correspondences, an international, peer-reviewed online journal devoted to the academic study of Western esotericism. By providing a wider forum of debate regarding issues and currents in Western esotericism than has previously been possible, Correspondences is committed to publishing work of a high academic standard as determined by a peer-review process, but does not require academic credentials as prerequisite for publication. Students and non-affiliated academics are encouraged to join established scholars in submitting insightful, well-researched articles that offer new ideas, positions, or information to the field

Correspondences - Online Journal For The Academic Study of Western Esotericism, Volume 6(1)

Welcome to Correspondences, an international, peer-reviewed online journal devoted to the academic study of Western esotericism. By providing a wider forum of debate regarding issues and currents in Western esotericism than has previously been possible, Correspondences is committed to publishing work of a high academic standard as determined by a peer-review process, but does not require academic credentials as prerequisite for publication. Students and non-affiliated academics are encouraged to join established scholars in submitting insightful, well-researched articles that offer new ideas, positions, or information to the field

Correspondences - Online Journal For The Academic Study of Western Esotericism, Volume 6(1)

Welcome to Correspondences, an international, peer-reviewed online journal devoted to the academic study of Western esotericism. By providing a wider forum of debate regarding issues and currents in Western esotericism than has previously been possible, Correspondences is committed to publishing work of a high academic standard as determined by a peer-review process, but does not require academic credentials as prerequisite for publication. Students and non-affiliated academics are encouraged to join established scholars in submitting insightful, well-researched articles that offer new ideas, positions, or information to the field

Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension

\ua9 2023, The Author(s).Introduction: In the event-driven FREEDOM-EV trial, oral treprostinil delayed clinical worsening in patients with pulmonary arterial hypertension (PAH). Open-label extension studies offer additional data about tolerability, efficacy, and survival, especially for those initially assigned placebo. The aim of the current study was to determine if oral treprostinil changed survival when considering the parent and extension study, if treprostinil provides functional benefits for participants initially assigned to placebo, and if the benefits observed for those treated with treprostinil were durable. Methods: Both active and placebo participants from FREEDOM-EV could enroll in the FREEDOM-EV open-label extension (OLE) study after experiencing an investigator-assessed clinical worsening event or after parent study closure. All participants in the OLE were offered open-label oral treprostinil. Previously assigned placebo participants titrated to maximally tolerated doses; previously assigned treprostinil participants continued dose titration. We repeated assessments including functional class and 6-min walk distance (6MWD) at 12-week intervals and measured N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 48. Survival was estimated by Kaplan–Meier analysis, and we estimated hazard ratio (HR) using Cox proportional hazards. Results: Of 690 FREEDOM-EV participants, 470 enrolled in the OLE; vital status was available for 89% of initial Freedom-EV participants. When considering the combined parent and open-label data, initial assignment to oral treprostinil reduced mortality (HR 0.64, 95% confidence interval 0.46–0.91, p = 0.013); absolute risk reduction was 9%. Participants randomized to placebo who initiated oral treprostinil after clinical worsening and tolerated treatment through week 48 demonstrated favorable shifts in functional class (p &lt; 0.0001), 6MWD improvements of + 84 m (p &lt; 0.0001), and a reduction in NT-proBNP of − 778 pg/mL (p = 0.02), compared to OLE baseline. Modest trends toward benefit were measured for those initially assigned placebo who did not have clinical worsening, and 132/144 (92%) of treprostinil assigned participants without clinical worsening remained on drug at week 48 in the OLE study. Adverse events were consistent with FREEDOM-EV. Conclusion: Initial treprostinil assignment improved survival in the entire data set; those who began treprostinil after a clinical worsening in the placebo arm and tolerated drug to week 48 enjoyed substantial functional gains. Clinical Trial Registration: ClinicalTrials.gov identifier NCT01560637

Reduced Serotonin Reuptake Transporter (SERT) Function Causes Insulin Resistance and Hepatic Steatosis Independent of Food Intake

Serotonin reuptake transporter (SERT) is a key regulator of serotonin neurotransmission and a major target of antidepressants. Antidepressants, such as selectively serotonin reuptake inhibitors (SSRIs), that block SERT function are known to affect food intake and body weight. Here, we provide genetic evidence that food intake and metabolism are regulated by separable mechanisms of SERT function. SERT-deficient mice ate less during both normal diet and high fat diet feeding. The reduced food intake was accompanied with markedly elevated plasma leptin levels. Despite reduced food intake, SERT-deficient mice exhibited glucose intolerance and insulin resistance, and progressively developed obesity and hepatic steatosis. Several lines of evidence indicate that the metabolic deficits of SERT-deficient mice are attributable to reduced insulin-sensitivity in peripheral tissues. First, SERT-deficient mice exhibited beta-cell hyperplasia and islet-mass expansion. Second, biochemical analyses revealed constitutively elevated JNK activity and diminished insulin-induced AKT activation in the liver of SERT-deficient mice. SERT-deficient mice exhibited hyper-JNK activity and hyperinsulinemia prior to the development of obesity. Third, enhancing AKT signaling by PTEN deficiency corrected glucose tolerance in SERT-deficient mice. These findings have potential implications for designing selective SERT drugs for weight control and the treatment of metabolic syndromes