Additive and global functions of HoxA cluster genes in mesoderm derivatives.

Hox genes encode transcription factors that play a central role in the specification of regional identities along the anterior to posterior body axis. In the developing mouse embryo, Hox genes from all four genomic clusters are involved in range of developmental processes, including the patterning of skeletal structures and the formation of several organs. However, the functional redundancy observed either between paralogous genes, or among neighboring genes from the same cluster, has hampered functional analyses, in particular when synergistic, cluster-specific functions are considered.

Diabetes in primary care: prospective associations between depression, nonadherence and glycemic control.

Background: Findings are inconsistent regarding the degree to which depression may exert a negative impact on glycemic control in patients with type 2 diabetes. We therefore aimed to examine the longitudinal relationship between depression, behavioral factors, and glycemic control.

Methods: In a prospective component of a nationally representative sample, 866 patients with type 2 diabetes aged >or=18 years completed a standardized assessment including a laboratory screening, questionnaires, and diagnostic measures.

BCL6 and BCoR gang up on Notch to regulate left-right patterning.

In this issue of Developmental Cell, Sakano et al. describe a novel mechanism of how a key lymphocyte transcription factor crosstalks to Notch signaling during embryonic development and thereby selectively inhibits Notch-activated target genes to allow proper left-right patterning.

Cancer stem cells at the crossroads of current cancer therapy failures--radiation oncology perspective.

Despite continuous improvements in cancer management, locoregional recurrence or metastatic spread still occurs in a high proportion of patients after radiotherapy or combined treatments. One underlying reason might be a low efficacy of current treatments on eradication of cancer stem cells (CSCs). It has been recognised for a long time, that only the small subpopulation of CSCs can cause recurrences and that all CSCs need to be killed for permanent tumour cure.

The validity of the German version of the Health of the Nation Outcome Scales (HoNOS-D): a clinician-rating for the differential assessment of the severity of mental disorders.

The Health of the Nation Outcome Scales (HoNOS) is an internationally-established clinician-rating instrument for the differential assessment of the severity of patients with mental disorders. The aim of this study was to examine the validity of the German version of the HoNOS (HoNOS-D). Evaluation of validity, including factor validity, convergent and discriminant validity and sensitivity to change, was conducted on a large, virtually representative, clinical sample of patients with mental disorders in inpatient psychotherapy (Study 1, N = 3169).

Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin.

Background: The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth.

The mental health of female sex workers.

Objective: There is limited information available about the mental health of female sex workers. Therefore, we aimed to make a comprehensive assessment of the mental status of female sex workers over different outdoors and indoors work settings and nationalities.

Method: As the prerequisites of a probability sampling were not given, a quota-sampling strategy was the best possible alternative.

[Psychooncological care for breast cancer patients in hospitals and in the outpatient sector].

Background: Psycho-oncological care is nowadays an integral part of patient-oriented health care in oncology. Psycho-oncological services are considered in the formulation of guidelines and the existence of such services is a precondition for the certification of organ centres.

Methods: For a status quo analysis of psycho-oncological health-care services for breast cancer patients in inpatient and outpatient care, 101 hospitals (inpatient care) and 124 health-care professionals in outpatient psycho-oncological services were questioned by mail.

[Evidence-based treatments in the rehabilitation of patients with depression--a literature review].

Background: In recent years, the importance of guidelines has increased continuously. This development also occurs in the field of rehabilitative health care, where process guidelines are being designed for various indicational groups to ensure quality standards and improvements.

Aim: The primary goal of this paper is to collect and evaluate the evidence for various treatment options for depressive disorders in order to establish a basis for the current development of a process guideline for the rehabilitation of patients with depressive disorders.

Novel P2-P4 macrocyclic inhibitors of HCV NS3/4A protease by P3 succinamide fragment depeptidization strategy.

Hepatitis C represents a serious worldwide health-care problem. Recently, we have disclosed a novel class of P2-P4 macrocyclic inhibitors of NS3/4A protease containing a carbamate functionality as capping group at the P3 N-terminus. Herein we report our work aimed at further depeptidizing the P3 region by replacement of the urethane function with a succinamide motif.

Dynamic regulation of notch 1 and notch 2 surface expression during T cell development and activation revealed by novel monoclonal antibodies.

It is well established that Notch signaling plays a critical role at multiple stages of T cell development and activation. However, detailed analysis of the cellular and molecular events associated with Notch signaling in T cells is hampered by the lack of reagents that can unambiguously measure cell surface Notch receptor expression. Using novel rat mAbs directed against the extracellular domains of Notch1 and Notch2, we find that Notch1 is already highly expressed on common lymphoid precursors in the bone marrow and remains at high levels during intrathymic maturation of CD4(-)CD8(-) thymocytes.

Validity of routine clinical DSM-IV diagnoses (Axis I/II) in inpatients with mental disorders.

The assessment of diagnoses is a central issue in the treatment of patients with mental disorders. The aim of this study was to validate routine clinical diagnoses by means of a semi-standardized and structured interview. Semi-standardized and structured interview diagnoses were based on videos of 55 inpatients.

Identification and biological evaluation of a series of 1H-benzo[de]isoquinoline-1,3(2H)-diones as hepatitis C virus NS5B polymerase inhibitors.

The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells and, as a consequence, is an attractive target for inhibition. Herein, we present 1H-benzo[de]isoquinoline-1,3(2H)-diones as a new series of selective inhibitors of HCV NS5B polymerase.

Novel macrocyclic inhibitors of hepatitis C NS3/4A protease featuring a 2-amino-1,3-thiazole as a P4 carbamate replacement.

Our laboratories recently reported the discovery of P2-P4 macrocyclic inhibitors of HCV NS3/4A protease, characterized by high levels of potency and liver exposure. Within this novel class of inhibitors, we here describe the identification of a structurally diverse series of compounds featuring a 2-amino-1,3-thiazole as replacement of the carbamate in P4. Optimization studies focused on structural modifications in the P3, P2, and P1 regions of the macrocycle as well as on the linker chain and resulted in the discovery of several analogues characterized by excellent levels of enzyme and cellular activity.

[Can quality of life in psychotherapy be measured with clinician-ratings? A comparison of patient- and clinician-ratings using the SF-8].

Objective: Quality of life is a major criterion of the outcome of psychotherapeutic interventions. The concept of quality of life emphasizes patient self-ratings. However, they can be burdensome or inappropriate in some cases.

[Psychosomatic rehabilitation: quo vadis?].

According to the latest research its effectiveness can be considered as proven. By now there are many evaluation studies that document the psychosomatic rehabilitation process itself as well as long-term results. In the wake of procedural optimization in medical rehabilitation, however, potential for further development has also been stated, in particular given an increasing number of psychosomatic patients and their heterogeneous disease patterns.

Depression, anxiety, post-traumatic stress disorder and health-related quality of life and its association with social support in ambulatory prostate cancer patients.

The aim of this study is to identify anxiety, depression and post-traumatic stress disorder in prostate cancer patients and to investigate the association with social support and health-related quality of life. A total of 511 men who had undergone prostatectomy were surveyed during ambulatory follow-up care for an average of 27 months after surgery using standardised self-report measures (e.g.

2-(3-Thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acids as inhibitors of HCV NS5B RdRp.

A series of 2-(3-thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acid inhibitors of the hepatitis C virus (HCV) NS5B polymerase enzyme are reported. Sulfonyl urea substituted analogs in this series proved to be the most potent active site non-nucleoside inhibitors of NS5B reported to date. These compounds had low nanomolar enzyme inhibition across HCV genotypes 1-3 and showed single digit micromolar inhibition in the HCV replicon assay.

Sensory deprivation regulates the development of the hyperpolarization-activated current in auditory brainstem neurons.

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are highly expressed in the superior olivary complex, the primary locus for binaural information processing. This hyperpolarization-activated current (I(h)) regulates the excitability of neurons and enhances the temporally precise analysis of the binaural acoustic cues. By using the whole-cell patch-clamp technique, we examined the properties of I(h) current in neurons of the lateral superior olive (LSO) and the medial nucleus of the trapezoid body (MNTB) before and after hearing onset.

[The potential performance of developmental screenings in kindergarten. Characteristics and circulation of currently available instruments in Germany].

The German institutions of elementary education, such as the kindergarten, are to perform developmental assessments for pre-school children in order to address specific need for interventions. Currently available assessment tools for the use by kindergarten staff were collected and compared according to scientific, economic and practical usability criteria based upon research and users expectations. 20 assessment tools were found in the German psychology database PSYNDEX, in publications, Internet, and in 45 interviews with experts from the largest supplier organizations of kindergartens.

Optimization of thienopyrrole-based finger-loop inhibitors of the hepatitis C virus NS5B polymerase.

Infections caused by the hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The NS5B polymerase of HCV is responsible for the replication of viral RNA and has been a prime target in the search for novel treatment options. We had discovered allosteric finger-loop inhibitors based on a thieno[3,2-b]pyrrole scaffold as an alternative to the related indole inhibitors.

Serotonin targets inhibitory synapses to induce modulation of network functions.

The cellular effects of serotonin (5-HT), a neuromodulator with widespread influences in the central nervous system, have been investigated. Despite detailed knowledge about the molecular biology of cellular signalling, it is not possible to anticipate the responses of neuronal networks to a global action of 5-HT. Heterogeneous expression of various subtypes of serotonin receptors (5-HTR) in a variety of neurons differently equipped with cell-specific transmitter receptors and ion channel assemblies can provoke diverse cellular reactions resulting in various forms of network adjustment and, hence, motor behaviour.