Psilocybin’s Effects on Neuritogenesis in Cancer Associated Neurons

https://openworks.mdanderson.org/sumexp23/1034/thumbnail.jp

Targeting Nociceptive and Cholinergic Nerves in Irradiated Oropharyngeal Cancer Model Reveals Novel Mechanism for Dysphagia

https://openworks.mdanderson.org/sumexp23/1038/thumbnail.jp

Recent Trends in Oral Anticoagulant Use and Post-Discharge Complications Among Atrial Fibrillation Patients with Acute Myocardial Infarction

Background: Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI).The CHA2DS2VAScand CHADS2risk scoresare used to identifypatients with AF at risk for strokeand to guide oral anticoagulants (OAC) use, including patients with AMI. However, the epidemiology of AF, further stratifiedaccording to patients\u27 risk of stroke, has not been wellcharacterized among those hospitalized for AMI. Methods: We examined trends in the frequency of AF, rates of discharge OAC use, and post-discharge outcomes among 6,627 residents of the Worcester, Massachusetts area who survived hospitalization for AMI at 11 medical centers between 1997 and 2011. Results: A total of 1,050AMI patients had AF (16%) andthe majority (91%)had a CHA2DS2VAScscore \u3e 2.AF rates were highest among patients in the highest stroke risk group.In comparison to patients without AF, patients with AMI and AF in the highest stroke risk category had higher rates of post-discharge complications, including higher 30-day re-hospitalization [27 % vs. 17 %], 30-day post-discharge death [10 % vs. 5%], and 1-year post-discharge death [46 % vs. 18 %] (p \u3c 0.001 for all). Notably, fewer than half of guideline-eligible AF patients received an OAC prescription at discharge. Usage rates for other evidence-based therapies such as statins and beta-blockers,lagged in comparison to AMI patients free from AF. Conclusions: Our findings highlight the need to enhance efforts towards stroke prevention among AMI survivors with AF

Can the Non-pneumatic Anti-Shock Garment (NASG) reduce adverse maternal outcomes from postpartum hemorrhage? Evidence from Egypt and Nigeria

<p>Abstract</p> <p>Background</p> <p>Postpartum hemorrhage (PPH) is the leading cause of maternal mortality and severe maternal morbidity. The Non-pneumatic Anti-Shock Garment (NASG), a first-aid lower-body compression device, may decrease adverse outcomes from obstetric hemorrhage. This article is the first to report the effect of the NASG for PPH.</p> <p>Methods</p> <p>This pre-intervention/NASG study of 854 women was conducted in four referral facilities in Nigeria and two in Egypt between 2004-2008. Entry criteria were women with PPH due to uterine atony, retained placenta, ruptured uterus, vaginal or cervical lacerations or placenta accreta with estimated blood loss of ≥ 750 mL and one clinical sign of shock. Differences in demographics, conditions on study entry, treatment and outcomes were examined. The Wilcoxon rank-sum test and relative risks with 95% confidence intervals were calculated for primary outcomes - measured blood loss, emergency hysterectomy, mortality, morbidity (each individually), and a combined variable, "adverse outcomes", defined as severe morbidity and mortality. A multiple logistic regression model was fitted to test the independent association between the NASG and the combined severe morbidity and mortality outcome.</p> <p>Results</p> <p>Measured blood loss decreased by 50% between phases; women experienced 400 mL of median blood loss after study entry in the pre-intervention and 200 mL in the NASG phase (p < 0.0001). As individual outcomes, mortality decreased from 9% pre-intervention to 3.1% in the NASG phase (RR 0.35, 95% CI 0.19-0.62); severe morbidity decreased from 4.2% to 1%, in the NASG phase (RR 0.24, 95% CI 0.09-0.67). As a combination, "adverse outcomes," decreased from 12.8% to 4.1% in the NASG phase (RR 0.32, 95% CI 0.19-0.53). In a multiple logistic regression model, the NASG was associated with the combined outcome of severe maternal morbidity and mortality (OR 0.42, 95% CI 0.18-0.99).</p> <p>Conclusion</p> <p>In this non-randomized study, in which bias is inherent, the NASG showed promise for reducing blood loss, emergency hysterectomy, morbidity and mortality associated with PPH in referral facilities in Egypt and Nigeria.</p

A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year ( with possible extension for responders). The dose was titrated according to serum calcium levels. The treatment effect was evaluated by regular CT scans. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted for 29 and at least 36 months ( patient still in remission when data censored). Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 mug of Seocalcitol. This is the first study showing activity, by reduction in tumour dimensions, of a differentiating agent in patients with an advanced bulky, solid tumour. Seocalcitol may have an effect in the treatment of HCC, especially in early disease when a prolonged treatment can be instituted. The survival benefit with or without tumour response should be determined in controlled studies

Serum 25-Hydroxyvitamin D Concentrations and Season-Specific Correlates in Japanese Adults

Background: Several lines of evidence indicate an important role for vitamin D in the prevention of a range of diseases. Blood vitamin D levels show clear seasonal variation; however, data on the determinants of vitamin D status for each season are limited. We investigated the association between lifestyle and serum vitamin D concentration by season in Japanese workers. Methods: Subjects were 312 men and 217 women aged 21 to 67 years who worked in municipal offices in Northern Kyushu, Japan and participated in a periodic checkup in July or November. Multiple linear regression analysis was used to examine the association between serum 25-hydroxivitamin D concentrations and lifestyle factors for each season. Results: Mean serum 25-hydroxyvitamin D concentration was 27.4 ng/ml (68.4 nmol/L) and 21.4 ng/ml (53.4 nmol/L) for workers surveyed in July and November, respectively (P \u3c 0.001); the prevalence of vitamin D deficiency ( both sexes) and nonsmoking and physical activity (in men) were significantly associated with higher concentrations of serum 25-hydroxyvitamin D. In summer, fish/shellfish intake was associated with higher serum 25- hydroxyvitamin D concentrations in women. Conclusions: Vitamin D deficiency is common in Japanese workers during seasons with limited sunlight. The lifestyle correlates of favorable vitamin D status in November were physical activity, dietary vitamin D intake, and nonsmoking

Alternative Oxidase Mediates Pathogen Resistance in Paracoccidioides brasiliensis Infection

Thermally dimorphic pathogenic fungi are responsible for potentially life-threatening diseases of immunocompetent and immunocompromised individuals. These microorganisms grow as conidia-producing mycelia in the environment, which when inhaled by the host convert to the pathogenic yeast form at 37°C. During adaptation and growth, fungi interact with host immune cells and must cope with defense mechanisms such as imposed-oxidative stress (e.g., reactive oxygen species; ROS). Alternative oxidase (AOX) is an enzyme recently implicated in the reduction of ROS production by the mitochondria when triggered by external stimuli, such as temperature and ROS. During this work we have evaluated the relevance of AOX during infection with Paracoccidioides brasiliensis, the etiological agent of one of the most prevalent mycoses in Latin America, paracoccidioidomycosis. We show that PbAOX gene expression is stimulated after interaction with alveolar macrophages or in the presence of H2O2 and is essential for survival against fungicidal activity of both the immune cells and the ROS compound. Moreover, decreasing PbAOX gene expression in P. brasiliensis led to increased survival of infected mice. Altogether, our data supports a relevant role for AOX in the virulence of P. brasiliensis

Association between the rs6950982 polymorphism near the SERPINE1 gene and blood pressure and lipid parameters in a high-cardiovascular-risk population: interaction with Mediterranean diet

The SERPINE1 (serpin peptidase inhibitor, clade E, member 1) gene, better known by its previous symbol PAI-1 (plasminogen activator inhibitor 1), has been associated with cardiovascular phenotypes with differing results. Our aim was to examine the association between the rs6950982 (G > A) near the SERPINE1 gene, blood pressure (BP) and plasma lipid concentrations as well as the modulation of the polymorphism effects by adherence to Mediterranean diet (AMD). We studied 945 high-cardiovascular-risk subjects. Biochemical, clinical, dietary and genetic data (rs6950982) were obtained. We also determined the common rs1799768 (4G/5G), for checking independent effects. AMD was measured by a validated questionnaire, and four groups were considered. rs6950982 (A > G) and rs1799768 (4G/5G) were only in moderate–low linkage disequilibrium (D′ = 0.719; r2 = 0.167). The most significant associations we obtained were with rs6950982 (A > G). In males, the G allele was nominally associated with higher diastolic BP (AA: 81.5 ± 10.9, AG: 82.1 ± 11.4, GG: 85.7 ± 10.5 mmHg; Padditive = 0.030) and systolic BP (AA + AG: 141.4 ± 6.9 mmHg vs. GG: 149.8 ± 8.0 mmHg; Precessive = 0.036). In the whole population, the rs6950982 was also associated with plasma lipids. Subject with the G allele presented higher total cholesterol (Padditive = 0.016, Precessive = 0.011), low-density lipoprotein cholesterol (Padditive = 0.032, Precessive = 0.031) and triglycerides (Padditive = 0.040, Precessive = 0.029). AMD modulated the effect of rs6950982 on triglyceride concentrations (P for interaction = 0.036). Greater AMD reduced the higher triglyceride concentrations in GG subjects. No significant interactions were found for the other parameters. The rs6950982 was associated with higher BP in men and higher triglycerides in the whole population, this association being modulated by AMD

Pregnancy after bariatric surgery: Consensus recommendations for periconception, antenatal and postnatal care

The objective of the study is to provide evidence‐based guidance on nutritional management and optimal care for pregnancy after bariatric surgery. A consensus meeting of international and multidisciplinary experts was held to identify relevant research questions in relation to pregnancy after bariatric surgery. A systematic search of available literature was performed, and the ADAPTE protocol for guideline development followed. All available evidence was graded and further discussed during group meetings to formulate recommendations. Where evidence of sufficient quality was lacking, the group made consensus recommendations based on expert clinical experience. The main outcome measures are timing of pregnancy, contraceptive choice, nutritional advice and supplementation, clinical follow‐up of pregnancy, and breastfeeding. We provide recommendations for periconception, antenatal, and postnatal care for women following surgery. These recommendations are summarized in a table and print‐friendly format. Women of reproductive age with a history of bariatric surgery should receive specialized care regarding their reproductive health. Many recommendations are not supported by high‐quality evidence and warrant further research. These areas are highlighted in the paper