Help-seeking by substance dependants presenting to healthcare professionals in the Free State Province

Introduction. Current data regarding treatment needs in South Africa for substance dependence are based on admissions to specialised treatment centres. The data therefore do not include patients presenting to independent healthcare workers and state hospitals. Aim. The aim of this study was to investigate help-seeking behaviour for substance dependence disorders from the perspective of healthcare professionals at various levels of the referral chain in Free State Province. Design. A descriptive study was performed. Setting. Treatment environments in Free State Province accessible to substance-dependent persons. Participants. General practitioners, private psychiatrists, prescribing healthcare professionals at state hospitals and treatment centres, and non-prescribing therapists responsible for management of substance-dependent persons. Measurements. A questionnaire was used to determine the level of help-seeking experienced by the participants regarding various classes of psycho-active substances. Findings. The presentation of alcohol, cannabis, opioid, benzodiazepine, ecstasy, cocaine and inhalant dependency at general practitioners, private psychiatrists, treatment centres and non-prescribing therapists was compared. Different patterns of help-seeking for substance dependence from the various professional groups were detected. Regarding alcohol dependence, 40.3% of private general medical practitioners reported being confronted with alcohol dependence at least once per month, compared with 100% of treatment centre representatives and private psychiatrists, 70.6% of state hospitals and 53.8% of non-prescribers. State hospitals reported the highest frequency for contact with cases of cannabis dependence, compared with the other professional groups, while psychiatrists reported the highest contact with cases involving benzodiazepine, cocaine and ecstasy. Therapists reported a higher level of contact with inhalant dependence, while this group virtually never presented at general practitioners and private psychiatrists. Conclusion. Help-seeking data can be used in conjunction with other data, such as treatment demand data, to inform and adapt policies and practice. Variations in the manifestation of help-seeking behaviour at various groups may be important pointers to conditions that influence help-seeking, and therefore should be investigated further

Identification of depression in a rural general practice

Major depression is underdiagnosed by general practitioners, but the reasons for this are not clear. This study aimed to establish the prevalence of major depression and coexisting generalised anxiety disorder in a rural general practice in the Orange Free State. It also assessed the predictive value of a screening questionnaire for use by general practitioners. The two practitioners evaluated 858 patients over a 4-week period. Those who met the screening criteria, together with a random sample of 60 patients who did not, were re-evaluated by a registrar in psychiatry who was unaware of the findings of his colleagues. Of the patients studied, 134 (15,6%) had major depression; 59 of these (44,0%) also had coexisting generalised anxiety disorder. The general practitioners had . correctly diagnosed major depression in 32 patients (3,7%) before the study started. The screening questionnaire had a 42% chance of correctly identifying a patient with depression and a 97% chance of correctly identifying a patient who did not have major depression. Both practitioners were equally capable at identifying major depression. The study confirmed both the high prevalence of depression in a rural general practice and its low identification rate. It also showed the advantage of using a screening questionnaire to alert practitioners to the possibility of depression in their patients

Environmental and Genetic Determinants of Colony Morphology in Yeast

Nutrient stresses trigger a variety of developmental switches in the budding yeast Saccharomyces cerevisiae. One of the least understood of such responses is the development of complex colony morphology, characterized by intricate, organized, and strain-specific patterns of colony growth and architecture. The genetic bases of this phenotype and the key environmental signals involved in its induction have heretofore remained poorly understood. By surveying multiple strain backgrounds and a large number of growth conditions, we show that limitation for fermentable carbon sources coupled with a rich nitrogen source is the primary trigger for the colony morphology response in budding yeast. Using knockout mutants and transposon-mediated mutagenesis, we demonstrate that two key signaling networks regulating this response are the filamentous growth MAP kinase cascade and the Ras-cAMP-PKA pathway. We further show synergistic epistasis between Rim15, a kinase involved in integration of nutrient signals, and other genes in these pathways. Ploidy, mating-type, and genotype-by-environment interactions also appear to play a role in the controlling colony morphology. Our study highlights the high degree of network reuse in this model eukaryote; yeast use the same core signaling pathways in multiple contexts to integrate information about environmental and physiological states and generate diverse developmental outputs

Integration of Global Signaling Pathways, cAMP-PKA, MAPK and TOR in the Regulation of FLO11

The budding yeast, Saccharomyces cerevisiae, responds to various environmental cues by invoking specific adaptive mechanisms for their survival. Under nitrogen limitation, S. cerevisiae undergoes a dimorphic filamentous transition called pseudohyphae, which helps the cell to forage for nutrients and reach an environment conducive for growth. This transition is governed by a complex network of signaling pathways, namely cAMP-PKA, MAPK and TOR, which controls the transcriptional activation of FLO11, a flocculin gene that encodes a cell wall protein. However, little is known about how these pathways co-ordinate to govern the conversion of nutritional availability into gene expression. Here, we have analyzed an integrative network comprised of cAMP-PKA, MAPK and TOR pathways with respect to the availability of nitrogen source using experimental and steady state modeling approach. Our experiments demonstrate that the steady state expression of FLO11 was bistable over a range of inducing ammonium sulphate concentration based on the preculturing condition. We also show that yeast switched from FLO11 expression to accumulation of trehalose, a STRE response controlled by a transcriptional activator Msn2/4, with decrease in the inducing concentration to complete starvation. Steady state analysis of the integrative network revealed the relationship between the environment, signaling cascades and the expression of FLO11. We demonstrate that the double negative feedback loop in TOR pathway can elicit a bistable response, to differentiate between vegetative growth, filamentous growth and STRE response. Negative feedback on TOR pathway function to restrict the expression of FLO11 under nitrogen starved condition and also with re-addition of nitrogen to starved cells. In general, we show that these global signaling pathways respond with specific sensitivity to regulate the expression of FLO11 under nitrogen limitation. The holistic steady state modeling approach of the integrative network revealed how the global signaling pathways could differentiate between multiple phenotypes

Tailor-Made Zinc-Finger Transcription Factors Activate FLO11 Gene Expression with Phenotypic Consequences in the Yeast Saccharomyces cerevisiae

Cys2His2 zinc fingers are eukaryotic DNA-binding motifs, capable of distinguishing different DNA sequences, and are suitable for engineering artificial transcription factors. In this work, we used the budding yeast Saccharomyces cerevisiae to study the ability of tailor-made zinc finger proteins to activate the expression of the FLO11 gene, with phenotypic consequences. Two three-finger peptides were identified, recognizing sites from the 5′ UTR of the FLO11 gene with nanomolar DNA-binding affinity. The three-finger domains and their combined six-finger motif, recognizing an 18-bp site, were fused to the activation domain of VP16 or VP64. These transcription factor constructs retained their DNA-binding ability, with the six-finger ones being the highest in affinity. However, when expressed in haploid yeast cells, only one three-finger recombinant transcription factor was able to activate the expression of FLO11 efficiently. Unlike in the wild-type, cells with such transcriptional activation displayed invasive growth and biofilm formation, without any requirement for glucose depletion. The VP16 and VP64 domains appeared to act equally well in the activation of FLO11 expression, with comparable effects in phenotypic alteration. We conclude that the functional activity of tailor-made transcription factors in cells is not easily predicted by the in vitro DNA-binding activity

Cryptococcus neoformans Mediator Protein Ssn8 Negatively Regulates Diverse Physiological Processes and Is Required for Virulence

Cryptococcus neoformans is a ubiquitously distributed human pathogen. It is also a model system for studying fungal virulence, physiology and differentiation. Light is known to inhibit sexual development via the evolutionarily conserved white collar proteins in C. neoformans. To dissect molecular mechanisms regulating this process, we have identified the SSN8 gene whose mutation suppresses the light-dependent CWC1 overexpression phenotype. Characterization of sex-related phenotypes revealed that Ssn8 functions as a negative regulator in both heterothallic a-α mating and same-sex mating processes. In addition, Ssn8 is involved in the suppression of other physiological processes including invasive growth, and production of capsule and melanin. Interestingly, Ssn8 is also required for the maintenance of cell wall integrity and virulence. Our gene expression studies confirmed that deletion of SSN8 results in de-repression of genes involved in sexual development and melanization. Epistatic and yeast two hybrid studies suggest that C. neoformans Ssn8 plays critical roles downstream of the Cpk1 MAPK cascade and Ste12 and possibly resides at one of the major branches downstream of the Cwc complex in the light-mediated sexual development pathway. Taken together, our studies demonstrate that the conserved Mediator protein Ssn8 functions as a global regulator which negatively regulates diverse physiological and developmental processes and is required for virulence in C. neoformans

Endocrine responses after thyrotrophin-releasing hormone stimulation and dexamethasone suppression tests in the major depressive syndrome

CITATION: Aalbers, C., Taljaard, J.J.F. & Gagiano, C.A. 1986. Endocrine responses after thyrotrophin-releasing hormone stimulation and dexamethasone suppression tests in the major depressive syndrome. S Afr Med J, 70(4):464-468.The original publication is available at http://www.samj.org.zaThe effects of dexamethasone 1 mg on plasma cortisol levels and of thyrotrophin-releasing hormone (TRH) 200 μg on thyrotrophin (TSH), growth hormone and prolactine levels in 107 patients with a major depressive disorder (MDD) were compared with those in 87 healthy subjects. Individual hormonal responses and combinations of hormonal responses after administration of dexamethasone and TRH were evaluated as diagnostic aids for MDD by calculating sensitivity, specificity and efficiency for single and multiple hormonal abnormalities. In patients suffering from MDD, 65% of men, 74% of reproductive women and 71% of menopausal or hysterectomized (H/M) women had abnormal responses (sensitivity) to a dexamethasone suppression test (DST). When the DST and TSH responses to TRH were combined, 85% of men, 87% of reproductive women and 84% of H/M women had abnormal results. If the efficiency of the different combinations of hormone responses is calculated, a totally different picture emerges.Publisher’s versio

The functional dissection of Mss11p, a transcription factor regulating pseudohyphal differentiation, invasive growth and starch metabolism in <I>Saccharomyces cerevisiae</I>.

AgriwetenskappeInstituut Vir WynbiotegnologiePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]