Cyclic adenosine monophosphate (cAMP) is a master regulator of mitochondrial metabolism but its precise mechanism of action yet remains unclear. Here, we found that a dietary saturated fatty acid ...(FA), palmitate increased intracellular cAMP synthesis through the palmitoylation of soluble adenylyl cyclase in cardiomyocytes. cAMP further induced exchange protein directly activated by cyclic AMP 1 (Epac1) activation, which was upregulated in the myocardium of obese patients. Epac1 enhanced the activity of a key enzyme regulating mitochondrial FA uptake, carnitine palmitoyltransferase 1. Consistently, pharmacological or genetic Epac1 inhibition prevented lipid overload, increased FA oxidation (FAO), and protected against mitochondrial dysfunction in cardiomyocytes. In addition, analysis of Epac1 phosphoproteome led us to identify two key mitochondrial enzymes of the the β-oxidation cycle as targets of Epac1, the long-chain FA acyl-CoA dehydrogenase (ACADL) and the 3-ketoacyl-CoA thiolase (3-KAT). Epac1 formed molecular complexes with the Ca
/calmodulin-dependent protein kinase II (CaMKII), which phosphorylated ACADL and 3-KAT at specific amino acid residues to decrease lipid oxidation. The Epac1-CaMKII axis also interacted with the α subunit of ATP synthase, thereby further impairing mitochondrial energetics. Altogether, these findings indicate that Epac1 disrupts the balance between mitochondrial FA uptake and oxidation leading to lipid accumulation and mitochondrial dysfunction, and ultimately cardiomyocyte death.
Tissue engineering chambers (TECs) bring great hope in regenerative medicine as they allow the growth of adipose tissue for soft tissue reconstruction. To date, a wide range of TEC prototypes are ...available with different conceptions and volumes. Here, we addressed the influence of TEC design on fat flap growth in vivo as well as the possibility of using bioresorbable polymers for optimum TEC conception. In rats, adipose tissue growth is quicker under perforated TEC printed in polylactic acid than non-perforated ones (growth difference 3 to 5 times greater within 90 days). Histological analysis reveals the presence of viable adipocytes under a moderate (less than 15% of the flap volume) fibrous capsule infiltrated with CD68
inflammatory cells. CD31-positive vascular cells are more abundant at the peripheral zone than in the central part of the fat flap. Cells in the TEC exhibit a specific metabolic profile of functional adipocytes identified by
H-NMR. Regardless of the percentage of TEC porosity, the presence of a flat base allowed the growth of a larger fat volume (p < 0.05) as evidenced by MRI images. In pigs, bioresorbable TEC in poly1,4-dioxane-2,5-dione (polyglycolic acid) PURASORB PGS allows fat flap growth up to 75 000 mm
at day 90, (corresponding to more than a 140% volume increase) while at the same time the TEC is largely resorbed. No systemic inflammatory response was observed. Histologically, the expansion of adipose tissue resulted mainly from an increase in the number of adipocytes rather than cell hypertrophy. Adipose tissue is surrounded by perfused blood vessels and encased in a thin fibrous connective tissue containing patches of CD163
inflammatory cells. Our large preclinical evaluation defined the appropriate design for 3D-printable bioresorbable TECs and thus opens perspectives for further clinical applications.
The purpose of the study was to describe the pattern of 99mTc-labeled phosphate agents myocardial uptake by scintigraphy and explore its impact on left ventricular (LV) functions in transthyretin ...cardiac amyloidosis (TTR-CA).
Fifty patients with TTR-CA underwent 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy and echocardiography with measure of LV thickness, longitudinal strain (LS), systolic and diastolic functions. Cardiac retention by scintigraphy was assessed by visual scoring and the heart/whole body (H/WB) ratio was calculated by dividing counts in the heart by counts in late whole-body images.
The mean population age was 79 ± 10 years. Mean H/WB ratio was 12 ± 7. Myocardial 99mTc-HMDP uptake on segments 5, 6, 7, 8, 11, 12, 13, 14, 16, and 17 was correlated with H/WB ratio. Mean LVEF and global LS were 51 ± 10% and − 10 ± 3%, respectively. H/WB ratio was correlated with global LS (R = 0.408, P = .003), Ea (R = − 0.566, P < .001) and mean left ventricular wall thickness (R = 0.476, P < .001) but not with LVEF (R = − 0.109, P = .453). Segmental myocardial uptake was slightly correlated with segmental LS (R = 0.152, P < .001). H/WB ratio was not correlated with NT-proBNP levels (R = 0.219, P = .148) neither E/Ea ratio (R = 0.204, P = .184).
These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis.
Purpose
We aimed to compare different methods for semi-quantitative analysis of cardiac retention of bone tracers in patients with cardiac transthyretin amyloidosis (ATTR).
Methods
Data from 67 ...patients with ATTR who underwent both conventional whole-body scan and a CZT myocardial SPECT (DSPECT, Spectrum Dynamics) 3 h after injection of
99m
Tc-labeled bone tracer were analyzed. Visual scoring of cardiac retention was performed on whole-body scan according to Perugini 4-point grading system from 0 (no uptake) to 3 (strong cardiac uptake with mild/absent bone uptake). A planar heart-to-background (H:B) ratio was calculated using whole-body scan (wb-H:B). CZT SPECT was quantified using three methods: planar H:B ratio calculated from anterior reprojection (ant-H:B), left anterior oblique reprojection (LAO-H:B), and 3D-H:B ratio calculated from transaxial slices as mean counts in a VOI encompassing the heart divided by background VOI in the contralateral lung. Interventricular septal thickness was obtained using echocardiography.
Results
H:Bs obtained from planar and reprojected data were not statistically different (wb-H:B, 2.05 ± 0.64, ant-H:B, 1.97 ± 0.61, LAO-H:B, 2.06 ± 0.64, all
p
= ns). However, 3D-H:B was increased compared to planar H:Bs (3D-H:B, 4.06 ± 1.77, all
p
< 0.0001 vs. wb-H:B, ant-H:B, and LAO-H:B). Bland-Altman plots demonstrated that the difference between 3D and planar H:Bs increased with the mean value of myocardial uptake. 3D-H:B was best correlated to septal thickness (
r
= 0.45,
p
< 0.001). Finally, abnormal right ventricular uptake was associated with higher values of cardiac retention.
Conclusion
3D semi-quantitative analysis of CZT SPECT optimized the assessment of
99m
Tc-labeled bone tracer myocardial uptake in patients with cardiac amyloidosis.
Our study aimed to assess the prevalence of post-traumatic stress disorder (PTSD) after childbirth one year after vaginal delivery and to identify characteristics of women and deliveries associated ...with it. Questionnaires were mailed a year after delivery to 1103 women with prospectively collected delivery and postpartum data, including a question on day 2 assessing their experience of childbirth. PTSD was assessed a year later by the Impact of Event and Traumatic Event Scales; 22 women (4.2%, 95%CI 2.7-6.3%) met the PTSD diagnostic criteria and 30 (5.7%; 95%CI 3.9-8.0%) PTSD profile criteria. Factors associated with higher risk of PTSD profile were previous abortion (aOR 3.6, 95%CI 1.4-9.3), previous postpartum hemorrhage (Aor 5.3, 95%CI 1.3-21.4), and postpartum hemoglobin <9 g/dl (aOR 2.7, 95%CI 1.0-7.5). Among 56 women (10.3%) reporting bad childbirth memories at day 2 postpartum, 11 (21.1%) met PTSD diagnosis and 11 (21.1%) PTSD profile criteria a year later, compared with 11 (2.4%) (P < 0.001) and 18 (3.8%) (P < 0.001), respectively, of the 489 (87.7%) women with good memories. PTSD is not rare at one year after vaginal delivery in a low-risk population. A simple question at day 2 post partum may identify women most at risk of PTSD and help determine if early intervention is needed.
Postpartum hemorrhage (PPH) is one of the leading causes of maternal death and severe maternal morbidity worldwide and strategies to prevent and treat PPH vary among international authorities. Areas ...covered: This review seeks to provide a global overview of PPH (incidence, causes, risk factors), prevention (active management of the third stage of labor and prohemostatic agents), treatment (first, second and third-line measures to control PPH), by also underlining recommendations elaborated by international authorities and using algorithms. Expert commentary: When available, oxytocin is considered the drug of first choice for both prevention and treatment of PPH, while peripartum hysterectomy remains the ultimate life-saving procedure if pharmacological and resuscitation measures fail. Nevertheless, the level of evidence for preventing and treating PPH is globally low. The emergency nature of PPH makes randomized controlled trials (RCT) logistically difficult. Population-based observational studies should be encouraged as they can usefully strengthen the evidence base, particularly for components of PPH treatment that are difficult or impossible to assess through RCT.
BACKGROUNDThere has been a shift to implement human rights-based approaches in acute mental health care due to increasing concerns around quality of care. National Health Service (NHS) Trusts have a ...legal duty to uphold a person's human rights, therefore it is important to understand what any barriers might be. Using psychological theory may help to develop this understanding. AIMTo test whether the theory of planned behaviour can be an effective model in understanding mental health professionals' intentions to work using a human rights-based approach. METHODParticipants were recruited from two NHS Trusts in the North West of England. A cross-sectional, survey design was used to examine mental health professionals' intentions to use human rights-based approaches. RESULTSMultiple regression analyses were performed on the theory of planned behaviour constructs showing that attitude and subjective norm significantly predicted intention. Perceived behavioural control did not add any significant variance, nor any demographic variables. CONCLUSIONThere could be factors outside of the individual clinician's control to fully work within a human rights-based framework on acute mental health wards. The theory of planned behaviour offers some understanding, however further development work into measuring human rights outcomes on acute mental health wards is needed.
To evaluate the effect of the fetal head station at attempted operative vaginal delivery (aOVD), and specifically midpelvic or low aOVD, on female and male sexual function and symptoms of postpartum ...depression (PPD) at 6 months.
Prospective population-based cohort study.
1,941 women with singleton term fetuses in vertex presentation with midpelvic or low aOVD between 2008 and 2013 in a tertiary care university hospital.
Symptoms of female sexual dysfunction using the Pelvic Organ Prolapse/Urinary Incontinence/Sexual Function Short Form Questionnaire (PISQ-12), symptoms of PPD using the Edinburgh Postnatal Depression Scale (EPDS) score, symptoms of male sexual dysfunction using the International Index of Erectile Function (IIEF-15) and perineal pain were assessed 6 months after aOVD. We measured the association between midpelvic or low aOVD and symptoms of female and male sexual function and symptoms of PPD at 6 months using multiple regression and adjusting for demographics, and risk factors of sexual dysfunction, symptoms of PPD and perineal pain with adjusted odds ratios (aORs) and 95% confidence intervals (95% CI).
The study included 907 women (46.7%) who responded to the questionnaire; 18.4% (167/907) had midpelvic aOVD, and 81.6% (740/907) low. Most women (873/907 96.3%) of those with partners reported sexual activity at 6 months. No significant difference was observed for PISQ-12, EPDS, IIEF-15 scores and perineal pain between mid and low pelvic groups. Compared with low pelvic aOVD, midpelvic aOVD was not significantly associated with either female or male sexual dysfunction (p = 0.89 and p = 0.76, respectively), or maternal symptoms of PPD (p = 0.83). Perineal pain significantly increased the risk of male and female sexual dysfunction and maternal symptoms of PPD at 6 months (p = 0.02, p = 0.006, and p = 0.02, respectively).
Midpelvic compared with low pelvic aOVD was not associated with an increase in sexual dysfunction, nor with symptoms of PPD at 6 months.
Abstract In France, 60,000 neonates are born preterm every year (7.4%), half of them after the spontaneous onset of labor. Among preventable risk factors of spontaneous prematurity, only cessation of ...smoking is associated with decreased prematurity (level of evidence LE1). It is therefore recommended (Grade A). Routine screening and treatment of vaginal bacteriosis is not recommended in the general population (Grade A). The only population for which vaginal progesterone is recommended is that comprising asymptomatic women with singleton pregnancies, no history of preterm delivery, and a short cervix at 16 to 24 weeks of gestation (Grade B). A history-indicated cerclage is not recommended for women with only a history of conization (Grade C), uterine malformation (professional consensus), isolated history of preterm delivery (Grade B), or twin pregnancies for primary (Grade B) or secondary (Grade C) prevention of preterm birth. A history-indicated cerclage is recommended for a singleton pregnancy with a history of at least 3 late miscarriages or preterm deliveries (Grade A). Ultrasound cervical length screening is recommended between 16 and 22 weeks for women with a singleton previously delivered before 34 weeks gestation, so that cerclage can be offered if cervical length <25 mm before 24 weeks (Grade C). A cervical pessary is not recommended for the prevention of preterm birth in a general population of asymptomatic women with twin pregnancies (Grade A) or in populations of asymptomatic women with a short cervix (professional consensus). Although the implementation of universal screening by transvaginal ultrasound for cervical length at 18–24 weeks of gestation in women with a singleton gestation and no history of preterm birth can be considered by individual practitioners, this screening cannot be universally recommended. In cases of preterm labor, (i) it is not possible to recommend any one of the several methods (ultrasound of the cervical length, vaginal examination, or fetal fibronectin assay) over any other to predict preterm birth (Grade B); (ii) routine antibiotic therapy is not recommended (Grade A); (iii) prolonged hospitalization (Grade B) and bed rest (Grade C) are not recommended. Compared with placebo, tocolytics are not associated with a reduction in neonatal mortality or morbidity (LE2) and maternal severe adverse effects may occur with all tocolytics (LE4). Atosiban and nifedipine (Grade B), unlike beta-agonists (Grade C), can be used for tocolysis in spontaneous preterm labor without preterm premature rupture of membranes. Maintenance tocolysis is not recommended (Grade B). Antenatal corticosteroid administration is recommended for all women at risk of preterm delivery before 34 weeks of gestation (Grade A). After 34 weeks, the evidence is insufficiently consistent to justify recommending systematic antenatal corticosteroid treatment (Grade B), but a course of this treatment might be indicated in clinical situations associated with high risk of severe respiratory distress syndrome, mainly in case of planned cesarean delivery (Grade C). Repeated courses of antenatal corticosteroids are not recommended (Grade A). Rescue courses are not recommended (Professional consensus). Magnesium sulfate administration is recommended for women at high risk of imminent preterm birth before 32 weeks (Grade A). Cesareans are not recommended for fetuses in vertex presentation (professional consensus). Both planned vaginal and elective cesarean delivery are possible for breech presentations (professional consensus). Delayed cord clamping may be considered if the neonatal or maternal state allows (professional consensus).
Three studies examined associations between goal disengagement and goal reengagement tendencies and indicators of physical health (e.g., health problems, cortisol rhythms, sleep efficiency). Based on ...research showing that goal adjustment tendencies are associated with subjective well-being, the authors predicted that people who are better able to disengage from unattainable goals and reengage with alternative goals also may experience better physical health. Across the three studies, the findings demonstrate that the ability to disengage from unattainable goals is associated with better self-reported health and more normative patterns of diurnal cortisol secretion. Goal reengagement, by contrast, was unrelated to indicators of physical health but buffered some of the adverse effects of difficulty with goal disengagement. The results also indicate that subjective well-being can mediate the associations between goal disengagement tendencies and physical health.
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