Glucocorticoid mechanisms of functional connectivity changes in stress-related neuropsychiatric disorders

AbstractStress—especially chronic, uncontrollable stress—is an important risk factor for many neuropsychiatric disorders. The underlying mechanisms are complex and multifactorial, but they involve correlated changes in structural and functional measures of neuronal connectivity within cortical microcircuits and across neuroanatomically distributed brain networks. Here, we review evidence from animal models and human neuroimaging studies implicating stress-associated changes in functional connectivity in the pathogenesis of PTSD, depression, and other neuropsychiatric conditions. Changes in fMRI measures of corticocortical connectivity across distributed networks may be caused by specific structural alterations that have been observed in the prefrontal cortex, hippocampus, and other vulnerable brain regions. These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms. Recent work indicates that circadian glucocorticoid oscillations act to balance synapse formation and pruning after learning and during development, and chronic stress disrupts this balance. We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders

Effects of feeding sainfoin proanthocyanidins to lactating ewes on intake, milk production and plasma metabolites; 34996024

There is increasing interest in using sainfoin (Onobrychis viciifolia) to feed sheep, but it contains proanthocyanidins (PACs), and the associated effects of PAC on sheep production are not well-known. The aim of the study was to assess the effect of the presence of PAC from sainfoin, through the inclusion of polyethylene glycol (PEG), on the intake and productive parameters of local ewes bearing one male lamb. For the experiment, 20 ewes and their newborn male lambs were placed in individual indoor cages. All ewes were fed ad libitum fresh sainfoin plus 200 g/d barley. Twice daily, half of the ewes were orally dosed with only water (Sainfoin Group; n = 10), and the other half were orally dosed with 100 g/d PEG 4000 per ewe (Sainfoin + PEG Group; n = 10). Sucking lambs were permanently housed with their dams until they reached 10–12 kg BW. The intake of sainfoin was recorded daily, and its chemical composition was analysed. Weekly, the BW, body condition score (BCS), milk yields and individual milk and blood samples were recorded. At the beginning and end of the experiment, faecal samples were collected from ewes and analysed for the anthelmintic role of PAC. The chemical composition, polyphenol content and antioxidant capacity of the diet and milk were analysed. The presence of PAC did not affect the intake, BW, BCS or milk yield of the dams (P > 0.05); however, all parameters were affected by the week of lactation (P 0.05). The presence of PAC had no effect on parasitism (P > 0.05). In conclusion, the presence of PAC had no relevant effects on milk production, although it affected protein metabolism, as indicated by the urea contents in milk and plasma. © 2021 The Author

Effects of condensed tannins from sainfoin on the milk fatty acid profile of ewes.

Abstract M136 There is an increased interest in using local fodder legumes to improve the self-sufficiency of feed for livestock. Sainfoin (Onobrychis viciifolia) is a typical high-quality crop of Mediterranean areas with a medium-high content of condensed tannins (CT), however their effects on milk composition are not well known. The aim of the study was to evaluate the effect of CT from fresh sainfoin on milk production, chemical composition, and fatty acids during 4 wk of lactation. Twenty pairs dam-lamb were individually fed fresh sainfoin ad libitum plus 200 g/d of barley. The distribution of pairs dam-lamb were done according to ewe’s BW (60.7 ± 6.15 kg BW) and BCS (3.3 ± 0.57), lambing date (06/04/2019 ± 0.95) and lamb weight at birth (4.1 ± 0.64 kg BW). Half of the ewes were daily orally dosed 100 g of PEG 4000/200 mL water per ewe as a tannin-binding agent (SF+PEG) and the other half received only water (SF). Once a week, ewes were milked and samples of sainfoin and milk were obtained and analyzed for chemical composition and individual fatty acids (FAs). The total saturated FA (SFA), monounsaturated FA (MUFA), polyunsaturated FA (PUFA), PUFA n-3 and PUFA n-6 were calculated. The sums and the major FA were analyzed using mixed models, with week of lactation as fixed and ewe as random effects using the SAS statistical software (SAS v.9.3)..

Pharmacokinetic control on the release of antimicrobial drugs from pH-responsive electrospun wound dressings

The acidic pH of healthy skin changes during wound healing due to the exposure of the inner dermal and subcutaneous tissue and due to the potential colonization of pathogenic bacteria. In chronic non-healing wounds, the pH values vary in a wide pH range but the appearance of an alkaline shift is common. After a wound is incurred, neutral pH in the wound bed is characteristic of the activation of the cascade of regenerative and remodeling processes. In order to adjust drug release to the specific pH of the wound, herein, drug-loaded wound dressings having pH-responsiveness containing antiseptics and antibiotics and exerting different release kinetics in order to have a perfect match between the drug release kinetics, and the pH conditions of each wound type, were developed. We have fabricated drug-loaded electrospun nanofibers loaded with the antiseptic chlorhexidine, with the broad-spectrum antibiotic rifampicin, and with the antimicrobial of natural origin thymol, using the pH-dependent methacrylic acid copolymer Eudragit® L100-55, which dissolves at pH > 5.5; those drugs were loaded within Eudragit® S100, which dissolves at pH > 7 and, finally, within the methacrylic ester copolymer Eudragit® RS100 which is pH independent and slowly erodes and releases its contained cargo. The antibacterial action of those advanced wound dressings has been evaluated against methicillin-sensitive S. aureus Newman strain expressing the coral green fluorescent protein (cGFP), as a model of a Gram-positive bacteria, and against E. coli S17 strain as a model of a Gram-negative bacteria. It was demonstrated that those combinational products integrate in one device the required characteristics for a wound dressing with the therapeutic action of a contained active principle and can be selected depending on the wound acidic or alkaline status for its appropriated management. © 2022 The Author(s

Réalités et enjeux de la participation des femmes dans les essais cliniques sur les antirétroviraux : expérience au Sénégal

De plus en plus d'essais cliniques se déroulent dans les pays du Sud. Contrairement aux pays du Nord, où dans les années 1990 les associations critiquaient l'absence de femmes dans les essais, les femmes sont quatre fois plus nombreuses que les hommes parmi les participants lors du dernier d'entre eux mené à Dakar. Cela rend particulièrement aiguë la question de la survenue de grossesses dans les essais. Ce chapitre analyse cette féminisation des participants aux essais, avec la question de savoir si celle-ci résulte des modalités d'inclusion. Le mode de prise en charge des femmes enceintes dans les essais sera présenté et discuté à partir de l'expérience des femmes, des soignants et des chercheurs. Les problèmes que pose la féminisation des participants aux essais cliniques seront discutés, notamment pour ce qui concerne les limites du dispositif de prise en charge en matière de contraception, les dispositions éthiques exigées et la possibilité de critères d'inclusion basés sur le sexe

Bile acid synthesis precursors in subjects with genetic hypercholesterolemia negative for LDLR/APOB/PCSK9/APOE mutations. Association with lipids and carotid atherosclerosis

Some oxysterols are precursors of bile acid synthesis and play an important role in cholesterol homeostasis. However, if they are involved in the pathogeny of genetic hypercholesterolemia has not been previously explored. We have studied non-cholesterol sterol markers of cholesterol synthesis (lanosterol and desmosterol) and oxysterols (7a-hydroxy-4-cholesten-3-one, 24S-hydroxycholesterol and 27-hydroxycholesterol) in 200 affected subjects with primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH) and 100 normolipemic controls. All studied oxysterols and cholesterol synthesis markers were significantly higher in affected subjects than controls (P < 0.001). Ratios of oxysterols to total cholesterol were higher in non-FH GH than in controls, although only 24S-hydroxycholesterol showed statistical significance (P < 0.001). Cholesterol synthesis markers had a positive correlation with BMI, triglycerides, cholesterol and apoB in control population. However, these correlations disappeared in non-FH GH with the exception of a weak positive correlation for non-HDL cholesterol and apoB. The same pattern was observed for oxysterols with high positive correlation in controls and absence of correlation for non-FH GH, except non-HDL cholesterol for 24S-hydroxycholesterol and 27-hydroxycholesterol and apoB for 27-hydroxycholesterol. All non-cholesterol sterols had positive correlation among them in patients and in controls. A total of 65 (32.5%) and 35 (17.5%) affected subjects presented values of oxysterols ratios to total cholesterol above the 95th percentile of the normal distribution (24S-hydroxycholesterol and 27-hydroxycholesterol, respectively). Those patients with the highest levels of 24S-hydroxycholesterol associated an increase in the carotid intima media thickness. These results suggest that bile acid metabolism is affected in some patients with primary hypercholesterolemia of genetic origin, negative for mutations in the candidate genes, and may confer a higher cardiovascular risk. Our results confirm that cholesterol synthesis overproduction is a primary defect in non-HF GH and suggest that subjects with non-FH GH show high levels of oxysterols in response to hepatic overproduction of cholesterol

Ruptured abdominal infrarenal aortic aneurysms - surgical treatment and outcome

Emergency Institute Of Cardiovascular Diseases ”Prof.Dr.C.C. Iliescu” Vascular Surgery Department, Bucharest, Romania, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Repair of ruptured abdominal aortic aneurysm carries a considerable rate of morbidity and mortality. Management of ruptured abdominal aortic aneurysms demands immediate diagnosis and a trained team to assess and deliver operative care, as well as logistic support in a dedicated center. Materials and method: Our experience consists of 63 cases of ruptured abdominal aortic aneurysm repair (2004- June 2011) - 57 males (90,5%) and 6 females (9,5%). There were 61 infrarenal abdominal aortic aneurysms (96,8%) and 2 thoracoabdominal aneurysms (3,2%). 35 patients were admitted in hemorrhagic shock (55,5%) and 38 were hemodynamically stable (45,5%). Results: We encountered 7 intraoperative deaths (11,1%), 19 postoperative deaths (30,1%) and 37 patients with long term survival (58,7%).Conclusions: Ruptured abdominal aortic aneurysm is a life-threatening condition that requires emergent surgery, followed by significant perioperative mortality and morbidity

Different protein composition of low-calorie diet differently impacts adipokine profile irrespective of weight loss in overweight and obese women

Background and aims: High-protein (HP) diets have shown benefits in cardiometabolic markers such as insulin or triglycerides but the responsible mechanisms are not known. We aimed to assess the effect of three energy-restricted diets with different protein contents (20%, 27%, and 35%; similar to 80% coming from animal source) on plasma adipokine concentration and its association with changes in cardiometabolic markers. Methods: Seventy-six women (BMI 32.8 +/- 2.93) were randomized to one of three calorie-reduced diets, with protein, 20%, 27%, or 35%; carbohydrates, 50%, 43%, or 35%; and fat, 30%, for 3 months. Plasma adipokine (leptin, resistin, adiponectin, and retinol-binding protein 4; RBP4) levels were assessed. Results: After 3 months, leptin concentration decreased in all groups without differences among them, while resistin levels remained unchanged. Adiponectin concentration heterogeneously changed in all groups (P for trend = 0.165) and resistin concentration did not significantly change. RPB4 significantly decreased by -17.5% (-31.7, -3.22) in 35%-protein diet (P for trend = 0.024 among diets). Triglycerides improved in women following the 35%-protein diet regardless of weight loss; RBP4 variation significantly influenced triglyceride concentration change by 24.9% and 25.9% when comparing 27%- and 35%- with 20%-protein diet, respectively. Conclusions: A 35%-protein diet induced a decrease in RBP4 regardless of weight loss, which was directly associated with triglyceride concentration improvement. These findings suggest that HP diets improve the cardiometabolic profile, at least in part, through changes in adipokine secretion. Whether this beneficial effect of HP diet is due to improvements in hepatic or adipose tissue functionality should be elucidated