Teaching to Relax: Development of a Program to Potentiate Stress-Results of a Feasibility Study with Medical Undergraduate Students.

Medical students are a population at risk for the development of stress-related risk states (e.g. burnout) and manifest mental disorders (e.g. depression). Still the learning of coping mechanisms against stress is not an integral part of the medical curriculum. In a pilot study we developed an elective course for learning relaxation techniques (Relacs) which was geared to the clinical practice of autogenic training (AT) with psychiatric patients. The course focussed on an innovative and mostly communicative transfer of knowledge about AT, progressive muscle relaxation and medical hypnosis and stressed the principle of repeated and supervised exercises in small student groups alongside self-administered exercise. 42 students took part in this course and showed a very high acceptance for the topic and positive evaluation. Moreover, we found a distinct improvement of the participants' mental parameters (burnout, anxiety) and a good knowledge about the course's contents within the final exams at the end of the semester. The structure and realisation of the course is easily adaptable and very effective regarding the improvement of the students' mental health. Due to our results and the commonly known prevalence of stress-related disorders in medical students we postulate the integration of courses on relaxation strategies in the medical curriculum.

[Development and correlation of work-related behavior and experience patterns, burnout and quality of life in medical students from their freshmanship to the first state examination]. / Entwicklung und Zusammenhang von Arbeitsverhalten, Burnout-Beschwerden und Lebensqualität bei Studierenden der Humanmedizin vom Studienstart bis zum ersten Staatsexamen.

Symptoms of burnout are common among medical students. Although they usually start with a good health status, their condition deteriorates over the course of their studies. In our study ESTRELLAS we examined 530 medical students in the preclinical semesters with validated psychological questionnaires. The longer the students were studying, the more showed risky working habits. Cognitive and emotional burnout symptoms increased coincidentally in their intensity, whereas the mental quality of life continuously deteriorated. Medical students' cognitive and emotional burnout symptoms are constantly increasing from the beginning of their studies. Contemporaneously, the mental quality of life is deteriorating. This might be based on a drastic change towards risky working habits. We suggest to actively work against this process to keep our motivated students and prospective physicians productive and in good mental health.

Osteopontin is induced by TGF-ß2 and regulates metabolic cell activity in cultured human optic nerve head astrocytes.

The aqueous humor (AH) component transforming growth factor (TGF)-ß2 is strongly correlated to primary open-angle glaucoma (POAG), and was shown to up-regulate glaucoma-associated extracellular matrix (ECM) components, members of the ECM degradation system and heat shock proteins (HSP) in primary ocular cells. Here we present osteopontin (OPN) as a new TGF-ß2 responsive factor in cultured human optic nerve head (ONH) astrocytes. Activation was initially demonstrated by Oligo GEArray microarray and confirmed by semiquantitative (sq) RT-PCR, realtime RT-PCR and western blot. Expressions of most prevalent OPN receptors CD44 and integrin receptor subunits αV, α4, α 5, α6, α9, ß1, ß3 and ß5 by ONH astrocytes were shown by sqRT-PCR and immunofluorescence labeling. TGF-ß2 treatment did not affect their expression levels. OPN did not regulate gene expression of described TGF-ß2 targets shown by sqRT-PCR. In MTS-assays, OPN had a time- and dose-dependent stimulating effect on the metabolic activity of ONH astrocytes, whereas TGF-ß2 significantly reduced metabolism. OPN signaling via CD44 mediated a repressive outcome on metabolic activity, whereas signaling via integrin receptors resulted in a pro-metabolic effect. In summary, our findings characterize OPN as a TGF-ß2 responsive factor that is not involved in TGF-ß2 mediated ECM and HSP modulation, but affects the metabolic activity of astrocytes. A potential involvement in a protective response to TGF-ß2 triggered damage is indicated, but requires further investigation.

Changes of osteopontin in the aqueous humor of the DBA2/J glaucoma model correlated with optic nerve and RGC degenerations.

PURPOSE: To identify age-dependent regulated aqueous humor (AH) factors in DBA2/J (D2J) mice and to correlate them with optic nerve degeneration and intraocular pressure (IOP) by population and individual analysis. METHODS: AH samples of D2J mice aged 2 (n = 3), 7 (n = 5), and 10 months (n = 14) were analyzed by mouse cytokine antibody array. Ten-month samples were classified into eyes with (D2J+) or without (D2J-) optic neuropathy. Ten-month-old C57/Bl6 (B6; n = 13) and DBA2/Rj (D2Rj; n = 15) mice served as controls. IOP was recorded from 2 to 10 months. Individual AH osteopontin (OPN) was determined in 31 D2J eyes (10 months) and was correlated with optic neuropathy and IOP. OPN mRNA was detected by in situ hybridization. OPN blood plasma content of D2J and B6 was monitored from 8 to 10 months. Effect of OPN on cell survival in the ganglion cell layer (GCL) or metabolism was tested in ex vivo-cultured D2Rj eyes and murine neuronal precursors. RESULTS: In array analysis, OPN was detected in 10-month-old D2J mice only. They significantly differed between D2J- and D2J+ (P = 0.006). By Western blot analysis, a sevenfold OPN increase in D2J+ was determined compared with B6. Individual analysis confirmed the positive correlation of OPN with optic neuropathy. IOP was not correlated with OPN. OPN blood plasma contents steadily increased with age in D2J. OPN(+) cells were detected within the ciliary body of D2J, and OPN(+) RGCs were ≈30% reduced. OPN treatment inhibited cell degeneration within the GCL in ex vivo-cultured D2Rj eyes and increased the metabolic activity of neuronal precursor cells. CONCLUSIONS: OPN is an age-dependent increased AH factor associated with degeneration of the optic nerve in D2J mice. By modulating the metabolism of neuronal cells, deregulated levels of OPN could be involved in degenerative processes affecting RGCs or optic nerve axons in the D2J model.

[Technique for jones tube placement in lacimal drainage surgery]. / Technik zur Platzierung von Jones Tubes im Rahmen der Tränenwegschirurgie.

In certain cases, the use of a Jones Tube is necessary for lacrimal duct reconstruction. Although the principle is straight forward, the practical procedure can prove to be difficult. The procedure requires the resection of the medial bony wall of the lacrimal sac. We form a duct between the medial canthus and the nasal cavity using a 14 gauge canula. By removing the needle, the catheter remains in place and serves as a guide for the placement of the Jones Tube with the assistance of an obturator. Thus the duct is not lost and an additional puncture is unnecessary.

Reactivation of optic nerve head astrocytes by TGF-beta2 and H2O2 is accompanied by increased Hsp32 and Hsp47 expression.

PURPOSE: Histologic studies have previously demonstrated increased expression of small heat shock proteins (Hsps) in reactive optic nerve head (ONH) astrocytes of patients with glaucoma. Transforming growth factor (TGF)-beta2 and hydrogen peroxide (H(2)O(2)) are known to induce ONH astrocyte reactivation. The goal of the present study was to determine whether new potentially involved Hsps, such as Hsp32, -47, -60, and -70, are expressed in the reactivation process of ONH astrocytes mediated by TGF-beta2 and H(2)O(2). METHODS: Cultured human ONH astrocytes were treated with 1.0 ng/mL TGF-beta2 for up to 48 hours. In addition, the cells were exposed to 100, 200, or 400 microM H(2)O(2) for 1 hour. Expression of Hsp32, -47, -60, and -70 was examined by immunohistochemistry, real-time PCR, and Western blot analyses. RESULTS: Treatment with TGF-beta2 increased Hsp32 after 4 and 6 hours, whereas Hsp47 was upregulated after treatment with TGF-beta2 for 12, 24, and 48 hours. Exposure of the cells to H(2)O(2) could increase both Hsp32 and -47. No significant effects on the expression of Hsp60 and -70 were observed after treatment of the cells with TGF-beta2 or H(2)O(2). CONCLUSIONS: TGF-beta2 increased Hsp32 after short-term treatment and Hsp47 after longer periods in cultured human ONH astrocytes. H(2)O(2) increased both Hsp32 and -47 levels. No effects on Hsp60 and -70 levels were induced by TGF-beta2 and H(2)O(2). These results may provide further insights into the cellular stress responses of reactive human ONH astrocytes. Further extensive studies are needed to examine the potential roles of Hsps in the ONH of glaucomatous eyes.

The effect of TGF-beta2 on elastin, type VI collagen, and components of the proteolytic degradation system in human optic nerve astrocytes.

PURPOSE: To investigate the effect of transforming growth factor (TGF)-beta2 on the expression of (1) elastin and type VI collagen (ColVI), (2) extracellular matrix (ECM)-degrading matrix-metalloproteinases (MMPs) and regulators of their activity/activation, and (3) the involvement of connective tissue growth factor (CTGF) in the TGF-beta2-mediated regulations in cultured human type-1A and -1B optic nerve astrocytes. METHODS: Astrocytes were isolated from the optic nerves of 11 donors aged 19 to 62 years without a history of eye disease from the prelaminar (type 1B, five explants) or postlaminar (type 1A, six explants) region. Cultures of passages 3 to 5 were treated with 1 ng/mL recombinant human TGF-beta2 for 72 hours, and regulatory effects on the expression of elastin and the ColVI chains alpha1, alpha2, and alpha3; MMP-1, -2, -3, -7, -9, -12, and -13; tissue inhibitors of MMPs (TIMPs) -1, -2, and -3; plasminogen activator inhibitor 1 (PAI-1); and urokinase and tissue plasminogen activators (uPA, tPA) were initially analyzed by RT-PCR and confirmed and quantified by real-time PCR (rtPCR). The regulation of proteins was studied by Western blot analysis, and MMP-2 activity was assessed by gelatin zymography. The involvement of CTGF was tested by knockdown experiments with CTGF-small interfering (si)RNA. RESULTS: TGF-beta2 increased the expression of elastin (5X[rtPCR]/6X[WB]), ColVIalpha2 (3X/5X), ColVIalpha3 (7X/9X), MMP-2 (2X/2X), TIMP-1/-3 (1.5X/2X), and PAI-1 (8X/4X) compared to untreated controls. tPA was reduced to 0.5X. MMP-1, -3, -7, and -12 and TIMP-2 were expressed but were not responsive to TGF-beta2. MMP-9 and -13 and uPA were marginally expressed and close to the detection threshold. MMP-2 activity was significantly reduced in gelatin zymography. Transfection of CTGF-siRNA blocked TGF-beta2-mediated activation of elastin and ColVI but had no effect on MMP-2 and PAI-1 induction. Type 1A and 1B astrocytes reacted identically. CONCLUSIONS: TGF-beta2 induces expression of elastin and ColVI and thereby could contribute to the increase of type VI collagen fibers in the tissue septae and the elastotic changes typically observed in POAG. With the concurrent activation of TIMP-1 and -3 and PAI-1 and the repression of tPA, TGF-beta2 could negatively regulate the activity and activation of MMPs. This effect could further amplify ECM accumulation and elastosis.

Studies of the comparative in vitro toxicology of the cyanobacterial metabolite deoxycylindrospermopsin.

Cyanobacteria are capable of producing metabolites that are in some cases toxic to humans and other animals. Of these metabolites, the toxin cylindrospermopsin (CYN) is produced by a number of species of cyanobacteria including Cylindrospermopsis raciborskii, and its toxicity has been documented. The CYN analog deoxycylindrospermopsin (deoxyCYN) is commonly produced in varying proportions by the cyanobacteria that produce CYN. The toxicological profile of CYN suggests that it is primarily a hepatotoxin, but with the capacity to damage other organs and tissues. Limited in vivo information is available on the toxicity of deoxyCYN and suggests it to be of low potency. The aim of this research was to determine the comparative toxicology of deoxyCYN using in vitro systems. Using cell viability assays, it was shown that deoxyCYN had inhibitory effects on cell viability and proliferation of a similar magnitude to that of CYN. Morphological changes in deoxyCYN-treated cells were similar to those of CYN. Investigation of protein synthesis inhibition demonstrated that deoxyCYN was of similar potency to CYN. Inhibition of protein synthesis is an acknowledged mechanism of toxicity for CYN, and the results produced here suggest that deoxyCYN operates by similar toxicological mechanisms to CYN and that in vivo animal testing should be undertaken to clarify the potential for risk to humans from this toxin.