To compare the acromegaly mortality rates with those expected for the general population from studies published before and after 2008.
We performed a systematic review and included observational ...studies in which the number of deaths observed in acromegaly was compared with the expected mortality for the general population mortality observed/expected (O/E). The following electronic databases were used as our data sources: EMBASE, MEDLINE and LILACS. From the observed and expected deaths, we recalculated all standardized mortality ratios (SMR) and their respective confidence intervals (95% CI), which were plotted in a meta-analysis using the software RevMan 5.3.
We identified 2303 references, and 26 studies fulfilled our eligibility criteria. From the 17 studies published before 2008, the mortality in acromegaly was increased, while from the nine studies published after 2008, the mortality was not different from the general population (SMR: 1.35, CI: 0.99-1.85). In six studies where somatostatin analogs (SAs) were used as adjuvant treatment, acromegaly mortality was not increased (SMR: 0.98, CI: 0.83-1.15), whereas in series including only patients treated with surgery and/or radiotherapy, mortality was significantly higher (SMR: 2.11; CI: 1.54-2.91). In studies published before and after 2008, the mortality was not increased in patients who achieved biochemical control, while it was higher in those with active disease. Cancer has become a leader cause of deaths in acromegaly patients in the last decade, period in which life expectancy improved.
Mortality in acromegaly is normalized with biochemical control and decreased in the last decade with the more frequent use of SAs as adjuvant therapy. Increased life expectancy has been associated with more deaths due to cancer.
Efforts to translate sub-anesthetic ketamine infusions into widespread clinical use have centered around developing medications with comparable neurobiological activity, but with attenuated ...psychoactive effects so as to minimize the risk of behavioral toxicity and abuse liability. Converging lines of research, however, suggest that some of the psychoactive effects of sub-anesthetic ketamine may have therapeutic potential. Here, we assess whether a subset of these effects – the so-called mystical-type experience – mediates the effect of ketamine on craving and cocaine use in cocaine dependent research volunteers. We found that ketamine leads to significantly greater acute mystical-type effects (by Hood Mysticism Scale: HMS), dissociation (by Clinician Administered Dissociative States Scale: CADSS), and near-death experience phenomena (by the Near-Death Experience Scale: NDES), relative to the active control midazolam. HMS score, but not the CADSS or NDES score, was found to mediate the effect of ketamine on global improvement (decreased cocaine use and craving) over the post-infusion period. This is the first controlled study to show that mystical-type phenomena, long considered to have therapeutic potential, may work to impact decision-making and behavior in a sustained manner. These data suggest that an important direction for medication development is the identification of ketamine-like pharmacotherapy that is selectively psychoactive (as opposed to free of experiential effects entirely), so that mystical-type perspectival shifts are more reliably produced and factors lending to abuse or behavioral impairment are minimized. Future research can further clarify the relationship between medication-occasioned mystical-type effects and clinical benefit for different disorders.
This article is part of the Special Issue entitled ‘Psychedelics: New Doors, Altered Perceptions’.
•Prior data suggest that certain hallucinogen-related psychoactive effects may be therapeutic.•Mystical-type effects were found to mediate the anti-addiction benefits of ketamine.•The mystical-type effects of ketamine and related agents may have clinical relevance, and merit further study.
The Southwestern Atlantic harbors unique and relatively understudied reef systems, including the only atoll in South Atlantic: Rocas atoll. Located 230 km off the NE Brazilian coast, Rocas is formed ...by coralline red algae and vermetid mollusks, and is potentially one of the most "pristine" areas in Southwestern Atlantic. We provide the first comprehensive and integrative description of the fish and benthic communities inhabiting different shallow reef habitats of Rocas. We studied two contrasting tide pool habitats: open pools, which communicate with the open ocean even during low tides, thus more exposed to wave action; and closed pools, which remain isolated during low tide and are comparatively less exposed. Reef fish assemblages, benthic cover, algal turfs and fish feeding pressure on the benthos remarkably varied between open and closed pools. The planktivore Thalassoma noronhanum was the most abundant fish species in both habitats. In terms of biomass, the lemon shark Negaprion brevirostris and the omnivore Melichtys niger were dominant in open pools, while herbivorous fishes (mainly Acanthurus spp.) prevailed in closed pools. Overall benthic cover was dominated by algal turfs, composed of articulated calcareous algae in open pools and non-calcified algae in closed pools. Feeding pressure was dominated by acanthurids and was 10-fold lower in open pools than in closed pools. Besides different wave exposure conditions, such pattern could also be related to the presence of sharks in open pools, prompting herbivorous fish to feed more in closed pools. This might indirectly affect the structure of reef fish assemblages and benthic communities. The macroalgae Digenea simplex, which is uncommon in closed pools and abundant in the reef flat, was highly preferred in herbivory assays, indicating that herbivory by fishes might be shaping this distribution pattern. The variations in benthic and reef fish communities, and feeding pressure on the benthos between open and closed pools suggest that the dynamics in open pools is mostly driven by physical factors and the tolerance of organisms to harsh conditions, while in closed pools direct and indirect effects of species interactions also play an important role. Understanding the mechanisms shaping biological communities and how they scale-up to ecosystem functioning is particularly important on isolated near-pristine systems where natural processes can still be studied under limited human impact.
Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. ...Converging evidence suggests a single sub-anesthetic dose of the N-methyl-D-aspartate receptor antagonist ketamine may work to correct these neuroadaptations and restore motivation for non-drug rewards. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs money later, we found that ketamine, as compared to the control, significantly decreased cocaine self-administration by 67% relative to baseline at greater than 24 h post-infusion, the most robust reduction observed to date in human cocaine users and the first to involve mechanisms other than stimulant or dopamine agonist effects. These findings signal new directions in medication development for substance use disorders.
Phyllosilicates have interesting properties, such as high capacity of ion exchange, adsorption, physicochemical stability and low/null toxicity, and thus, they are a promising material in ...pharmaceutical studies. Olanzapine (OLZ), used in the treatment of schizophrenia, is a drug of high cost and low water solubility, which are an obstacle to its use. In this work, an oral delivery system was developed using phyllosilicate (PHY-NT) and OLZ together to increase its solubility. PHY-NT was synthesized by sol–gel method, and then, OLZ was adsorbed creating the system called PHY-NT:OLZ. Thermal analysis was performed to investigate possible interactions between olanzapine and phyllosilicate. a sharp endothermic peak at 468 K was observed, which corresponds to the melting process of OLZ. When OLZ was added to PHY-NT, this peak was absent, suggesting an efficient denaturation of its crystal lattice. FTIR spectroscopy and X-ray powder diffraction were performed as complementary techniques to adequately support thermal analysis results. The created system caused a considerable increase in OLZ dissolution efficiency, and more than 80 % of the drug was released from PHY-NT:OLZ after 20 min. Drug release was evaluated in vitro and showed a Fickian diffusion-based pattern. Thus, results suggest that PHY-NT can be used as an alternative to increase drug dissolution rate of OLZ, expanding applications of these materials.
The pseudo-ilmenite structure ABO
3
have been increasingly highlighted in the optoelectronic area. Nanoparticles of undoped lithium niobates (LiNbO
3
) and codoped with rare earths (LiNbO
3
: Dy
3+/
...Tb
3+
) were synthesized by the solid-state reaction method and calcined in a controlled way. The properties and structural changes of niobates were evaluated from data obtained in XRD and Rietveld refinement. The SEM-FEG micrographs showed different morphologies obtained (cubes, plates, tetrahedrons and polyhedra) according to the variation of the doping and co-doping process. Optical properties were measured and studied based on the results obtained from the UV-Vis spectrophotometer and photoluminescence assays. The photoluminescence presented by LiNbO
3
was associated with the existence of superficial defects in the particles, i.e., centers of recombination of photogenerated charges favorable to the property. The effect of concentration of dopants was investigated in properties photoluminescence. Photometric measurements (CRI, purity, CCT, LER) were analyzed and a modulation of the emitted color as a function of the concentration of the dopants. According to the obtained results, LiNbO
3
: Dy
3+
/Tb
3+
presents itself as a material with great potential in optical device applications.
Graphical Abstract
Abstract Background Sub-anesthetic ketamine infusions may benefit a variety of psychiatric disorders, including addiction. Though ketamine engenders transient alterations in consciousness, it is not ...known whether these alterations influence efficacy. This analysis evaluates the mystical-type effects of ketamine, which may have therapeutic potential according to prior research, and assesses whether these effects mediate improvements in dependence-related deficits, 24 h postinfusion. Methods Eight cocaine dependent individuals completed this double-blind, randomized, inpatient study. Three counter-balanced infusions separated by 48 h were received: lorazepam (2 mg) and two doses of ketamine (0.41 mg/kg and 0.71 mg/kg, with the former dose always preceding the latter). Infusions were followed within 15 min by measures of dissociation (Clinician Administered Dissociative Symptoms Scale: CADSS) and mystical-type effects (adapted from Hood's Mysticism Scale: HMS). At baseline and 24 h postinfusion, participants underwent assessments of motivation to stop cocaine (University of Rhode Island Change Assessment) and cue-induced craving (by visual analogue scale for cocaine craving during cue exposure). Results Ketamine led to significantly greater acute mystical-type effects (by HMS) relative to the active control lorazepam; ketamine 0.71 mg/kg was associated with significantly higher HMS scores than was the 0.41 mg/kg dose. HMS score, but not CADSS score, was found to mediate the effect of ketamine on motivation to quit cocaine 24 h postinfusion. Conclusions These findings suggest that psychological mechanisms may be involved in some of the anti-addiction benefits resulting from ketamine. Future research can evaluate whether the psychoactive effects of ketamine influence improvements in larger samples.
To examine whether combined testosterone replacement and exercise training (ET) therapies would potentiate the beneficial effects of isolated therapies on neurovascular control and muscle wasting in ...patients with heart failure (HF) with testosterone deficiency.
From January 10, 2010, through July 25, 2013, 39 male patients with HF, New York Heart Association functional class III, total testosterone level less than 249 ng/dL (to convert to nmol/L, multiply by .03467), and free testosterone level less than 131 pmol/L were randomized to training (4-month cycloergometer training), testosterone (intramuscular injection of testosterone undecylate for 4 months), and training + testosterone groups. Muscle sympathetic nerve activity was measured using microneurography, forearm blood flow using plethysmography, body composition using dual X-ray absorptiometry, and functional capacity using cardiopulmonary test. Skeletal muscle biopsy was performed in the vastus lateralis.
Muscle sympathetic nerve activity decreased in ET groups (training, P<.01; training + testosterone, P<.01), whereas no changes were observed in the testosterone group (P=.89). Forearm blood flow was similar in all groups. Lean mass increased in ET groups (training, P<.01; training + testosterone, P<.01), whereas lean mass decreased in the testosterone group (P<.01). The response of cross-sectional area of type I (P<.01) and type II (P<.05) fibers increased in the training + testosterone group as compared with the isolated testosterone group.
Our findings provide evidence for a superior effect of combined ET and testosterone replacement therapies on muscle sympathetic nerve activity, muscle wasting, and functional capacity in patients with HF with testosterone deficiency.
Bovine pericardium (BP) has been used as a biomaterial for several decades in many medical applications particularly due to its mechanical properties and the high collagen content. In the acellular ...form it favors faster tissue repair, providing a three-dimensional support for cellular and vascular events observed during tissue repair and due, to a low elastin content, may favor its use as a breast implant cover, resulting in a low possibility of contracture of the biomaterial, preventing the appearance of irregularities during the reconstruction process. Thus, the aim of this study was to evaluate, histomorphologically, the behavior of acellularized bovine pericardium (ABP) as a mammary implant cover in rats. For this purpose, 16 animals were divided into two groups, with eight animals at each biological point: 7 and 15 days after surgery. Of the 16 animals, 32 specimens were obtained: 16 in the experimental group (EG) and 16 in the control group (CG). Throughout this study, none of the studied groups had postoperative complications. Results: The histomorphological results showed, in the two biological points, both in the EG and in the CG, chronic inflammatory infiltrate, leukocyte fibrin exudate, formation of granulation tissue and deposition of collagen fibers, more evident in the EG, regressive along the biological points. At 15 days, the implanted ABP showed initial biointegration with the fibrous capsule and surrounding tissues of the recipient bed. Conclusion: These results indicate that the due to the observed favorable tissue response ABP may be of potential use as a breast implant cover.
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