Children's affect regulation during a disappointment: psychophysiological responses and relation to parent history of depression

Psychophysiological responses during affect regulation were examined in 57 children ages 3-9 years, 41 of whom had a parent history of childhood-onset depression (COD). During a structured laboratory task, children were given first a disappointing toy and then a desired toy. Frontal electroencephalogram (EEG) asymmetry, respiratory sinus arrhythmia (RSA), heart period, and heart period variability were measured during resting and task conditions. Affective and self-regulatory behaviors were coded from videotape. In 3-5-year olds, greater relative right frontal activity was associated with withdrawal behavior. High heart period was associated with approach behavior. Compared with children of psychiatrically healthy parents, children of parents with COD exhibited poor heart period recovery after disappointment. For children of parents with COD, greater relative left frontal activity was related to concurrent internalizing and externalizing problems, and low resting RSA was related to internalizing problems. Physiological responses associated with affect regulation may help identify children at risk for depression.     

After-effects of transcranial direct current stimulation (tDCS) on cortical spreading depression

Abnormal cortical excitability influences susceptibility to cortical spreading depression (CSD) in migraine. Because transcranial direct current stimulation (tDCS) is capable of inducing lasting changes of cortical excitability, we investigated the after-effects of tDCS on the propagation velocity of CSD in the rat. Twenty-five anesthetised rats received either anodal, cathodal or sham tDCS. The stimulation was applied for 20 min at a current strength of 200 microA after the recording of three baseline CSD measurements. Starting 5 min after tDCS, a further three CSDs were elicited and CSD velocity recorded at intervals of 20 min. tDCS and CSD recording was performed under anaesthesia with chloralose and urethane. As compared to the baseline velocity of 3.14 mm/min, anodal tDCS induced a significant increase of propagation velocity during the first post-tDCS recording (3.49 mm/min). In contrast to anodal tDCS, neither cathodal tDCS nor sham tDCS, which consisted of an initial ramped DC stimulation lasting only 20 s, showed a significant effect on CSD propagation velocity. As anodal tDCS is known to induce a lasting increase of cortical excitability in the clinical setting, our results support the notion that CSD propagation velocity reflects cortical excitability. Since cortical excitability and susceptibility to CSD is elevated in migraine patients, anodal tDCS - by increasing cortical excitability - might increase the probability of migraine attack in these patients, even beyond the end of its application.     

Cytokine-induced killer T cells kill immature dendritic cells by TCR-independent and perforin-dependent mechanisms

Cytokine-induced killer (CIK) cells are ex vivo, expanded T cells with proven anticancer activity in vitro and in vivo. However, their functional properties with the exception of their cancer cell-killing activity are largely unclear. Here, we show that CIK T cells recognize dendritic cells (DC), and although mature DC (mDC) induce CIK T cells to produce IFN-gamma, immature DC (iDC) are killed selectively by them. Moreover, CIK T cell activation by mDC and their destruction of iDC are independent of the TCR. The cytotoxicity of CIK T cells to iDC is perforin-dependent. Our data have revealed an important regulatory role of CIK cells.     

Molecular analysis of microdeletions of the Y chromosome in Venezuelan males with idiopathic infertility

Today infertility is a major health problem affecting about 10-20% of couples. A male factor is assumed to be responsible in about 50% of the infertile couples. The origin of reduced testicular sperm function is unknown in about 60-70% of cases. There are several causes of male infertility such as varicocele, spermatic duct obstruction, and endocrine disorders. Micro-deletions in the Yq are known to represent the pathogenic mechanisms for infertile males. Three different non-overlapping regions designated as AZFa, AZFb, and AZFc are located in interval 5-6 of Yq, and are associated with impaired spermatogenesis in humans. To determine the prevalence of Y chromosomal microdeletions in Venezuelan males with idiopathic infertility, chromosomal, seminal, histological and molecular analyses were carried out in 29 Venezuelan males with idiopathic azoospermia or oligoospermia. Y-microdeletions analyses were performed using a multiplex polymerase chain reaction (PCR)-based technique with 22 sequences-tagged-sites (STSs). One of 29 patients (3.4%) had Yq microdeletions on AZFc. The frequency of AZF microdeletions in Venezuelan patients was similar to other populations with different ethnical or geographical origin.     

Professionalism in medical education: an institutional challenge.

Despite considerable attention to professionalism in medical education nationwide, the majority of attention has focused on training medical students, and less on residents and faculty. Curricular formats are often didactic, removed from the clinical setting, and frequently focus on abstract concepts. As a result of a recent curricular innovation at the University of Washington School of Medicine (UWSOM) in which role-model faculty work with medical students in teaching and modeling clinical skills and professionalism, a new professionalism curriculum was developed for preclinical medical students. Through student feedback, that curriculum has changed over time, and has become more focused on the clinical encounter. This new and evolving curriculum has raised awareness of the existence of an "ecology of professionalism." In this ecological model, changes in the understanding of and attention to professionalism at one institutional level lead to changes at other levels. At the UWSOM, heightened attention to professionalism at the medical student level led to awareness of the need for increased attention to teaching and modeling professionalism among faculty, residents, and staff. This new understanding of professionalism as an institutional responsibility has helped UWSOM teachers and administrators recognize and promote mechanisms that create a "safe" environment for fostering professionalism. In such an institutional culture, students, residents, faculty, staff, and the institution itself are all held accountable for professional behavior, and improvement must be addressed at all levels.     

Tal1/Scl gene transduction using a lentiviral vector stimulates highly efficient hematopoietic cell differentiation from common marmoset (Callithrix jacchus) embryonic stem cells

The development of embryonic stem cell (ESC) therapies requires the establishment of efficient methods to differentiate ESCs into specific cell lineages. Here, we report the in vitro differentiation of common marmoset (CM) (Callithrix jacchus) ESCs into hematopoietic cells after exogenous gene transfer using vesicular stomatitis virus-glycoprotein-pseudotyped lentiviral vectors. We transduced hematopoietic genes, including tal1/scl, gata1, gata2, hoxB4, and lhx2, into CM ESCs. By immunochemical and morphological analyses, we demonstrated that overexpression of tal1/scl, but not the remaining genes, dramatically increased hematopoiesis of CM ESCs, resulting in multiple blood-cell lineages. Furthermore, flow cytometric analysis demonstrated that CD34, a hematopoietic stem/progenitor cell marker, was highly expressed in tal1/scl-overexpressing embryoid body cells. Similar results were obtained from three independent CM ESC lines. These results suggest that transduction of exogenous tal1/scl cDNA into ESCs is a promising method to induce the efficient differentiation of CM ESCs into hematopoietic stem/progenitor cells.     

Antimicrobial analysis of different root canal filling pastes used in pediatric dentistry by two experimental methods

The objective of this study was to compare, by two experimental methods, the antimicrobial efficacy of different root canal filling pastes used in pediatric dentistry. The tested materials were: Guedes-Pinto paste (GPP), zinc oxide-eugenol paste (OZEP), calcium hydroxide paste (CHP), chloramphenicol + tetracycline + zinc oxide and eugenol paste (CTZP) and Vitapex. Fiven microbial strains (S. aureus, E. faecalis, P. aeruginosa, B. subtilis and C. albicans) obtained from the American Type Culture Collection were inoculated in Brain Heart Infusion (BHI) and incubated at 37 degrees C for 24 h. For the direct exposure test (DET), 72 paper points were contaminated with the standard microbial suspensions and exposed to the root canal filling pastes for 1, 24, 48 and 72 h. The points were immersed in Letheen Broth (LB), followed by incubation at 37 degrees C for 48 h. An inoculum of 0.1 mL obtained from LB was then transferred to 7 mL of BHI, under identical incubations conditions and the microbial growth was evaluated. The pastes showed activity between 1 and 24 h, depending on the material. For the agar diffusion test (ADT), 30 Petri plates with 20 mL of BHI agar were inoculated with 0.1 mL of the microbial suspension, using sterile swabs that were spread on the medium. Three cavities were made in each agar plate (total = 90) and completely filled with one of the filling root canal pastes. The plates were pre-incubated for 1 h at room temperature and then incubated at 37 degrees C for 24 to 48 h. The inhibition zone around each well was recorded in mm. The complete antimicrobial effect in the direct exposure test was observed after 24 h on all microbial indicators. All root canal filling materials induced the formation of inhibition zones, except for Vitapex (range, 6.0-39.0 mm).     

Triple therapy in type 2 diabetes: insulin glargine or rosiglitazone added to combination therapy of sulfonylurea plus metformin in insulin-naive patients

OBJECTIVE: To evaluate the efficacy and safety of add-on insulin glargine versus rosiglitazone in insulin-na?ve patients with type 2 diabetes inadequately controlled on dual oral therapy with sulfonylurea plus metformin. RESEARCH DESIGN AND METHODS: In this 24-week multicenter, randomized, open-label, parallel trial, 217 patients (HbA(1c) [A1C] 7.5-11%, BMI >25 kg/m(2)) on > or =50% of maximal-dose sulfonylurea and metformin received add-on insulin glargine 10 units/day or rosiglitazone 4 mg/day. Insulin glargine was forced-titrated to target fasting plasma glucose (FPG) < or =5.5-6.7 mmol/l (< or =100-120 mg/dl), and rosiglitazone was increased to 8 mg/day any time after 6 weeks if FPG was >5.5 mmol/l. RESULTS: A1C improvements from baseline were similar in both groups (-1.7 vs. -1.5% for insulin glargine vs. rosiglitazone, respectively); however, when baseline A1C was >9.5%, the reduction of A1C with insulin glargine was greater than with rosiglitazone (P < 0.05). Insulin glargine yielded better FPG values than rosiglitazone (-3.6 +/- 0.23 vs. -2.6 +/- 0.22 mmol/l; P = 0.001). Insulin glargine final dose per day was 38 +/- 26 IU vs. 7.1 +/- 2 mg for rosiglitazone. Confirmed hypoglycemic events at plasma glucose <3.9 mmol/l (<70 mg/dl) were slightly greater for the insulin glargine group (n = 57) than for the rosiglitazone group (n = 47) (P = 0.0528). The calculated average rate per patient-year of a confirmed hypoglycemic event (<70 mg/dl), after adjusting for BMI, was 7.7 (95% CI 5.4-10.8) and 3.4 (2.3-5.0) for the insulin glargine and rosiglitazone groups, respectively (P = 0.0073). More patients in the insulin glargine group had confirmed nocturnal hypoglycemia of <3.9 mmol/l (P = 0.02) and <2.8 mmol/l (P < 0.05) than in the rosiglitazone group. Effects on total cholesterol, LDL cholesterol, and triglyceride levels from baseline to end point with insulin glargine (-4.4, -1.4, and -19.0%, respectively) contrasted with those of rosiglitazone (+10.1, +13.1, and +4.6%, respectively; P < 0.002). HDL cholesterol was unchanged with insulin glargine but increased with rosiglitazone by 4.4% (P < 0.05). Insulin glargine had less weight gain than rosiglitazone (1.6 +/- 0.4 vs. 3.0 +/- 0.4 kg; P = 0.02), fewer adverse events (7 vs. 29%; P = 0.0001), and no peripheral edema (0 vs. 12.5%). Insulin glargine saved $235/patient over 24 weeks compared with rosiglitazone. CONCLUSIONS: Low-dose insulin glargine combined with a sulfonylurea and metformin resulted in similar A1C improvements except for greater reductions in A1C when baseline was > or =9.5% compared with add-on maximum-dose rosiglitazone. Further, insulin glargine was associated with more hypoglycemia but less weight gain, no edema, and salutary lipid changes at a lower cost of therapy.     

Inhibitory effect of somatostatin on inflammation and nociception

The present review focuses on promising new opportunities for anti-inflammatory and analgesic therapy. The theoretical background is an original observation based on our own experimental results. These data demonstrate that somatostatin is released from capsaicin-sensitive, peptidergic sensory nerve endings in response to noxious heat and chemical stimuli such as vanilloids, protons or lipoxygenase products. It reaches distant parts of the body via the circulation and exerts systemic anti-inflammatory and analgesic effects. Somatostatin binds to G-protein-coupled membrane receptors (sst(1)-sst(5)) and diminishes neurogenic inflammation by prejunctional action on sensory-efferent nerve terminals, as well as by postjunctional mechanisms on target cells. It decreases the release of pro-inflammatory neuropeptides from sensory nerve endings and also acts on receptors of vascular endothelial, inflammatory and immune cells. Analgesic effect is mediated by an inhibitory action on peripheral terminals of nociceptive neurons, since circulating somatostatin cannot exert central action. Somatostatin itself is not suitable for drug development because of its broad spectrum and short elimination half life, stable, receptor-selective agonists have been synthesized and investigated. The present overview is aimed at summarizing the physiological importance of somatostatin and sst receptors, pharmacological significance of synthetic agonists and their potential in the development of novel anti-inflammatory and analgesic drugs. These compounds might provide novel perspectives in the pharmacotherapy of acute and chronic painful inflammatory diseases, as well as neuropathic conditions.