Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Constraints On Frugivory By Bears

Bears consuming wild fruits for fall energy accumulation are constrained by several factors, including intake rate, the physiological capacity of the gastrointestinal tract, and the metabolic efficiency of gain in body mass. We measured these relationships through foraging and feeding trials using captive and wild black bears (Ursus americanus) and grizzly bears (Ursus arctos). Four fruit types covering a range of sizes and clustering were offered to captive bears to determine the effect of density, size, and presentation on intake rate. Intake rate (in grams per minute) and bite rates (in bites per minute) increased curvilinearly with increasing fruit density in singly spaced fruits. Maximum intakes ranged from 30 g/min for 0.5-g berries to \u3e200 g/min for 4.2-g fruits. The highest bite rates were obtained during the initial encounter with each patch as bears consumed all visually apparent fruits on the surface. Bite rates quickly dropped by 15-20% as foraging continued within the patch. Maximum bite rates were not depressed until initial fruit density fell to \u3c50 berries/M3. Maximum daily fresh fruit intake for the captive bears averaged 34 ± 6% (mean ± 1 SD) of body mass. The dry-matter digestibility of wild fruits, particularly preferred species, was as high as 72%. While large captive bears could gain body mass very rapidly when given fruit ad libitum, foraging efficiencies increasingly constrained growth rates of wild bears \u3e100 kg. We concluded that large bears, such as grizzlies, must depend on plants that permit large bite sizes or high bite rates through fruit clustering and bush configuration that reduce leaf-to-fruit ratios

Heat synchronization with Alfaprostol

One-hundred eighteen heifers were used to determine the effectiveness of Alfaprostol as a heat synchronization agent. Seventy-nine were injected twice (12 days apart) with 6 mg Alfaprostol per head and 39 were not treated. Twelve to 96 hours after the second injection 88.6% of the treated heifers were in standing heat and 81.4% of those in heat conceived at the first insemination. Eighty-one percent of the 37 untreated heifers in heat the first 21 days conceived at the first insemination. Ninety-one percent of the treated heifers and 89.2% of the untreated heifers conceived within a 50-day breeding period, so Alfaprostol did not affect reproductive performance

Glycoamino Acid Analogues of the Thomsen–Friedenreich Tumor-Associated Carbohydrate Antigen: Synthesis and Evaluation of Novel Antiproliferative Factor Glycopeptides

Glycoamino acid analogues of the Thomsen–Friedenreich antigen disaccharide, where the 4′ and 4″ hydroxyl groups were substituted with fluorine or hydrogen, were synthesized and incorporated into the asialylated antiproliferative factor (<i>as</i>-APF), a biologically active form of APF, a glycopeptide found in the urine of patients with interstitial cystitis. Various strategies were employed to incorporate the fluorine atom at the 4-positions of either the galactose or <i>N</i>-acetylgalactosamine unit of the disaccharide antigen, based on stereochemistry and reactivity. These glycopeptides were evaluated in antiproliferative assays on both primary normal bladder epithelial cells and T24 bladder carcinoma cells. Unlike many previously published substitutions to APF, mono-4′-fluorination of the GalNAc residue did not affect the activity, whereas fluoro-derivatives of the galactose 4″-position or both 4′ and 4″ hydroxyls showed a reduced potency relative to the monosubstituted GalNAc derivative. A fourth compound where the 4″ position of galactose was deoxygenated showed a lower potency than the parent and monosubstituted compounds. These results suggest that specific substitutions in the sugar moieties in the APF can be tolerated, and the glycomimetic design of APF analogues can include fluorine in the GalNAc sugar of the disaccharide

Christian Accommodative Mindfulness: Definition, Current Research, and Group Protocol

More clinicians are using mindfulness-based therapeutic strategies; however, Evangelical Christian clients sometimes worry about the Buddhist origins of these treatments. Christian accommodative mindfulness (CAM) attempts to address these concerns with culturally sensitive adaptations to mindfulness methods. We present a definition of CAM and propose some worldview adjustments to typical mindfulness constructs when working with these clients. The empirical research on Christian-derived meditation strategies and Christian-adapted mindfulness strategies will then be reviewed. We introduce a four-session group CAM protocol currently being researched that focuses on scripture meditation, breath meditation, body awareness, and loving-kindness meditation. Sample scripts are included

Emergency Department Discharge of Pulmonary Embolus Patients.

BACKGROUND: Hospitalization for low-risk pulmonary embolism (PE) is common, expensive, and of questionable benefit. OBJECTIVE: The objective was to determine if low-risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC). METHODS: Multicenter, open-label randomized trial in low-risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90-day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality. RESULTS: Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of -28.8 hours (95% confidence interval [CI] = -42.55 to -15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = -46.97 to -3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = -0.18 to 0.19). Total costs were $1,496 for early discharge and$4,234 for SOC, with a median difference of $2,496 (95$2,999 to -$2,151). CONCLUSIONS: Low-risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days

Emergency Department Discharge of Pulmonary Embolus Patients.

BACKGROUND: Hospitalization for low-risk pulmonary embolism (PE) is common, expensive, and of questionable benefit. OBJECTIVE: The objective was to determine if low-risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC). METHODS: Multicenter, open-label randomized trial in low-risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90-day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality. RESULTS: Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of -28.8 hours (95% confidence interval [CI] = -42.55 to -15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = -46.97 to -3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = -0.18 to 0.19). Total costs were $1,496 for early discharge and$4,234 for SOC, with a median difference of $2,496 (95$2,999 to -$2,151). CONCLUSIONS: Low-risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days