Psychosocial primary care – what patients expect from their General Practitioners A cross-sectional trial

BACKGROUND: Psychosocial Primary Care (PPC) is a model of service delivery for patients with mental disorders and psychosocial problems which was established in Germany in 1987. This study was performed as part of the evaluation of a PPC training program. We investigated patients' expectations of the psychosocial treatment offered by GPs trained in PPC. METHODS: Ten general practitioners trained in PPC were randomly selected. Two hundred and twenty patients were surveyed in the waiting room regarding their expectations concerning psychological treatment. RESULTS: Eighty-five per cent of patients could envisage making use of psychosocial treatments. Counselling by the GP was considered most important (65%). Fifty-four per cent of patients indicated that there was sufficient counselling, but further distinctions revealed dissatisfaction with both the extent and content of the counselling. Lack of time was the most frequent reason (53%) cited for insufficient counselling. A willingness to discuss the psychological aspects of illness was exhibited by between 55% (current illness) and 79% of patients. Two-thirds of patients believed that discussing psychological aspects and counselling by the doctor could exert a healing effect or contribute to symptomatic improvement in physical illnesses. Younger patients and patients with experience in psychotherapy expected referral to mental health services. CONCLUSIONS: Primary care patients desire and accept psychological treatment from their GP. Training in psychosocial competence in primary care should be offered more frequently

A Damage Mechanics Approach to Fatigue Assessment in Offshore Structures

This article is intended to describe the development of a fatigue damage model capable of assessing fatigue damage in offshore structures. This is achieved by for mulating a set of damage coupled constitutive and evolution equations which make the for mulation of a unified approach possible under both low and high cycle fatigue damage and consistent with the structural dynamic response of the changing/deteriorating material be haviors. The structural analysis for the whole designed period, say about 30 years, can be carried out with the aid of the proposed analytical procedure, in which the fundamental characteristics of sea wave statistics responsible for the structural dynamic response can be sufficiently considered. An offshore structure subject to complex ocean environment is described by a general stochastic system which embeds a group of stochastic subsystems, each characterizing a duty cycle. An effective analytical method is established by introduc ing the concept of duty strain range with a clear mathematical definition and its analytical solution which covers all possible spectral parameters. The history-dependent damage is also included in the damage model so that the overload effects can be analyzed. It should be pointed out that the whole procedure can be fully computerized such that the practical or engineering significance of varying design variables can be readily highlighted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67255/2/10.1177_105678959300200405.pd

Efflux in Fungi: La Pièce de Résistance

Pathogens must be able to overcome both host defenses and antimicrobial treatment in order to successfully infect and maintain colonization of the host. One way fungi accomplish this feat and overcome intercellular toxin accumulation is efflux pumps, in particular ATP-binding cassette transporters and transporters of the major facilitator superfamily. Members of these two superfamilies remove many toxic compounds by coupling transport with ATP hydrolysis or a proton gradient, respectively. Fungal genomes encode a plethora of members of these families of transporters compared to other organisms. In this review we discuss the role these two fungal superfamilies of transporters play in virulence and resistance to antifungal agents. These efflux transporters are responsible not only for export of compounds involved in pathogenesis such as secondary metabolites, but also export of host-derived antimicrobial compounds. In addition, we examine the current knowledge of these transporters in resistance of pathogens to clinically relevant antifungal agents

Candida albicans AGE3, the Ortholog of the S. cerevisiae ARF-GAP-Encoding Gene GCS1, Is Required for Hyphal Growth and Drug Resistance

BACKGROUND: Hyphal growth and multidrug resistance of C. albicans are important features for virulence and antifungal therapy of this pathogenic fungus. METHODOLOGY/PRINCIPAL FINDINGS: Here we show by phenotypic complementation analysis that the C. albicans gene AGE3 is the functional ortholog of the yeast ARF-GAP-encoding gene GCS1. The finding that the gene is required for efficient endocytosis points to an important functional role of Age3p in endosomal compartments. Most C. albicans age3Delta mutant cells which grew as cell clusters under yeast growth conditions showed defects in filamentation under different hyphal growth conditions and were almost completely disabled for invasive filamentous growth. Under hyphal growth conditions only a fraction of age3Delta cells shows a wild-type-like polarization pattern of the actin cytoskeleton and lipid rafts. Moreover, age3Delta cells were highly susceptible to several unrelated toxic compounds including antifungal azole drugs. Irrespective of the AGE3 genotype, C-terminal fusions of GFP to the drug efflux pumps Cdr1p and Mdr1p were predominantly localized in the plasma membrane. Moreover, the plasma membranes of wild-type and age3Delta mutant cells contained similar amounts of Cdr1p, Cdr2p and Mdr1p. CONCLUSIONS/SIGNIFICANCE: The results indicate that the defect in sustaining filament elongation is probably caused by the failure of age3Delta cells to polarize the actin cytoskeleton and possibly of inefficient endocytosis. The high susceptibility of age3Delta cells to azoles is not caused by inefficient transport of efflux pumps to the cell membrane. A possible role of a vacuolar defect of age3Delta cells in drug susceptibility is proposed and discussed. In conclusion, our study shows that the ARF-GAP Age3p is required for hyphal growth which is an important virulence factor of C. albicans and essential for detoxification of azole drugs which are routinely used for antifungal therapy. Thus, it represents a promising antifungal drug target

A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease