Diastolic Function Study with Conventional and Pulsed Tissue Doppler Echocardiography Imaging in Acromegalic Patients

Acromegaly is associated with myocardial hypertrophy and it can progress to diastolic and systolic dysfunction. Purpose: To evaluate diastolic function in acromegalic patients through conventional echocardiography (CD) and tissue Doppler imaging (TDI). Methods: Seventeen acromegalic patients were submitted to CD and TDI, and early (E) and atriogenic (A) transmitral flow were evaluated in mitral, septal, and tricuspid regions. Results: In comparison with controls the means of conventional (1.06), septal (1.01), and tricuspid (0.98) E/A ratio were significantly lower in acromegalic patients. E/A ratio <1.0 was demonstrated in 41% and 49% of acromegalics by DC and TDI, respectively, with no statistical difference among the two methods. An inverse linear correlation was shown between mitral E/A ratio and acromegalic age (r =−0.7). Conclusion: In this study, DC and TDI were equally effective in demonstrating diastolic dysfunction, a common finding in acromegalic patients.     

What factors determine patients’ preference for tumour necrosis factor inhibitors in ankylosing spondylitis?

Tumour necrosis factor inhibitor (TNFi) therapy, either intravenous (IV) or subcutaneous (SQ), demonstrates similar efficacy in ankylosing spondylitis (AS). The objective of this study was to examine factors influencing patient preference of TNFi. Fifty-nine (79.7%) participants were male with mean age 43.9 years and disease duration of 22.0 years. Fifty-nine patients (79.7%) agreed with the statement ‘My doctor gave me a choice and I made a decision based on my personal preference’. Patients commenced first on IV TNFi most commonly cited reduced frequency of injections (96.6%), administration by a trained professional (89.7%) and use of infusion time for leisure activities (86.2%). Patients commenced on SQ TNFi cited flexibility with timing of treatment (80%), shortened administration time (73.3%) and the convenience of home therapy (73.3%). Shared clinical decision-making between clinicians and patients may be desirable for AS patients commencing TNFi therapy.     

Serum albumin protects from cytokine-induced pancreatic β cell death by a phosphoinositide 3-kinase-dependent mechanism

The present study was undertaken to investigate the biological activity of serum albumin when pancreatic β cells were challenged by cytokines and pro-apoptotic reactive oxygen species like H₂O₂. Culture of mouse islets or INS-1E β cells for 24 h in the presence of H₂O₂ (25 μmol/l) increased cell death. This demise was prevented by serum albumin, dependent on its free sulfhydryl group, emphasizing that albumin may scavenge H₂O₂ due to its antioxidant properties. Culture for 48 h with a cytokine mixture of IL-1β (160 pg/ml), IFN-γ (200 ng/ml), and TNF-α (2 ng/ml) revealed that albumin, also protected against cytokine-induced death of both mouse islets and INS-1E β cells. This protective effect against cytokine-induced β cell death was, however, not dependent on albumins free sulfhydryl group, but was inhibited by the phosphoinositide 3-kinase (PI3K) inhibitors LY294002 (25 μmol/l) and wortmannin (1 μmol/l), suggesting that albumin may rescue β cells from cytokine-induced cell death by activation of PI3K. In accordance, albumin stimulated phosphorylation of Akt, a down-stream target for PI3K. In conclusion, it is suggested that albumin may be a survival factor for pancreatic β cells through scavenging of reactive oxygen species and by PI3K-dependent activation of Akt.     

New Echocardiographic Techniques in the Evaluation of Left Ventricular Mechanics in Subclinical Thyroid Dysfunction

The new echocardiographic techniques for the study of physiopathological intramyocardial phenomena include video densitometry (VD), integrated backscatter (IBS), and color Doppler myocardial imaging (CDMI). Being more independent from cardiac load and from rotational and translational heart motion, these new sensible, noninvasive techniques such as CDMI and IBS show a real incremental value in comparison with conventional echocardiography and allow to detect subtle functional and textural abnormalities of intramural myocardium, partially undetectable by conventional two-dimensional Doppler echocardiography. Subclinical thyroid dysfunction (STD), both in its hypo- and hyperthyroidism form, has a relatively high prevalence in general population (9–15% with a lower percentage of adult males), hence it could be very useful to study more deeply heart involvement in these physiopathological conditions and understand the complex relationship between thyroid and heart. The use of these new ultrasonic techniques in subclinical hypothyroidism helps to detect the early simultaneous involvement of both cardiac cycle phases, which causes a decrease of intramyocardial contractility and an impairment of both active and passive phases of diastole. In subclinical hyperthyroidism, these new ultrasonic techniques permitted to discover more complex and different early cardiac abnormalities of both systolic and diastolic phases.     

Some intrusions in dietary reports by fourth-grade children are based on specific memories: data from a validation study of the effect of interview modality

In dietary recall for a specified target period, an intrusion denotes an item reported eaten that was not consumed during that period. Intrusions may denote items available during the specified period, items consumed during other periods, or items from general knowledge of dietary intake. To investigate a cognitive basis of intrusions, we analyzed data from a dietary-reporting validation study in which 69 fourth-grade children were observed eating 2 school meals (breakfast and lunch) and interviewed that evening about that day's intake in person or by telephone. Of 450 items reported eaten for school meals, 82 were intrusions. Observations and school food service production records were used to determine whether items denoted by intrusions were available in school food service environments on the interview day, as many as 3 school days prior to the interview day, and the day following the interview. Availability of items denoted by intrusions decreased backward over days from the interview day, and decreased from the interview day to the following day. Among 40 children who reported at least 1 intrusion, mean number of intrusions (controlling for number of items reported) increased as interviews occurred later in the week. These results are consistent with the idea that some intrusions are based on specific memories of items encountered but not eaten during the target period, or encountered before the target period. Other intrusions are likely based on general dietary knowledge. It may be possible to design interview techniques to reduce the occurrence of intrusions that are incorrectly based on specific memories.     

The mammalian target of rapamycin pathway as a potential target for cancer chemoprevention.

The mammalian target of rapamycin (mTOR) is a key signaling node coordinating cell cycle progression and cell growth in response to genetic, epigenetic, and environmental conditions. Pathways involved in mTOR signaling are dysregulated in precancerous human tissues. These findings, together with the intriguing possibility that mTOR suppression may be associated with antitumor actions of caloric restriction, suggest that mTOR signaling may be an important target for chemopreventive drugs.     

Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.