Collaboration between general practitioners (GPs) and mental healthcare professionals within the context of reforms in Quebec

Background In the context of the high prevalence and impact of mental disorders worldwide, and less than optimal utilisation of services and adequacy of care, strengthening primary mental healthcare should be a leading priority. This article assesses the state of collaboration among general practitioners (GPs), psychiatrists and psychosocial mental healthcare professionals, factors that enable and hinder shared care, and GPs’ perceptions of best practices in the management of mental disorders. A collaboration model is also developed.Methods The study employs a mixed-method approach, with emphasis on qualitative investigation. Drawing from a previous survey representative of the Quebec GP population, 60 GPs were selected for further investigation.Results Globally, GPs managed mental healthcare patients in solo practice in parallel or sequential follow-up with mental healthcare professionals. GPs cited psychologists and psychiatrists as their main partners. Numerous hindering factors associated with shared care were found: lack of resources (either professionals or services); long waiting times; lack of training, time and incentives for collaboration; and inappropriate GP payment modes. The ideal practice model includes GPs working in multidisciplinary group practice in their own settings. GPs recommended expanding psychosocial services and shared care to increase overall access and quality of care for these patients.Conclusion As increasing attention is devoted worldwide to the development of optimal integrated primary care, this article contributes to the discussion on mental healthcare service planning. A culture of collaboration has to be encouraged as comprehensive services and continuity of care are key recovery factors of patients with mental disorders.     

Differential activation of human TLR4 by Escherichia coli and Shigella flexneri 2a lipopolysaccharide: combined effects of lipid A acylation state and TLR4 polymorphisms on signaling

The lipid A of LPS activates TLR4 through an interaction with myeloid differentiation protein-2 (MD-2) and the degree of lipid A acylation affects TLR4 responsiveness. Two TLR4 single nucleotide polymorphisms (Asp299Gly and Thr399Ile) have been associated with LPS hyporesponsiveness. We hypothesized that the combination of hypoacylation and these single nucleotide polymorphisms would exhibit a compounded effect on TLR4 signaling. HEK293T transfectants expressing wild-type or polymorphic TLR4 were stimulated with Escherichia coli (predominantly hexaacylated lipid A) or Shigella flexneri 2a (a mixture of hexaacylated, pentaacylated, and predominantly tetraacylated lipid A) LPS, or hexaacylated vs pentaacylated synthetic lipid As. NF-kappaB-reporter activity was significantly lower in response to S. flexneri 2a than E. coli LPS and further decreased in polymorphic transfectants. Neither hexaacylated nor pentaacylated synthetic lipid A induced NF-kappaB activity in wild-type transfectants under the identical transfection conditions used for LPS; however, increasing human MD-2 expression rescued responsiveness to hexaacylated lipid A only, while murine MD-2 was required to elicit a response to pentaacylated lipid A. Adherent PBMC of healthy volunteers were also compared for LPS-induced TNF-alpha, IL-6, IL-1beta, and IL-10 production. Cytokine levels were significantly lower (approximately 20-90%) in response to S. flexneri than to E. coli LPS/lipid A and PBMC from polymorphic individuals secreted decreased cytokine levels in response to both LPS types and failed to respond to pentaacylated lipid A. Thus, the combination of acylation state and host genetics may significantly impact vaccine immunogenicity and/or efficacy, whether LPS is an integral component of a whole organism vaccine or included as an adjuvant.     

Regulatory CD4+ T cells are crucial for preventing CD8+ T cell-mediated autoimmunity

In vivo studies have shown that regulatory CD4(+) T cells regulate conventional CD4(+) T cell responses to self- and environmental Ags. However, it remains unclear whether regulatory CD4(+) T cells control CD8(+) T cell responses to self, directly, or indirectly by decreasing available CD4(+) T cell help. We have developed an experimental mouse model in which suppressive and helper T cells cannot mediate their functions. The mouse chimeras generated were not viable and rapidly developed multiple organ autoimmunity. These features were correlated with strong CD8(+) T cell activation and accumulation in both lymphoid and nonlymphoid organs. In vivo Ab treatment and secondary transfer experiments demonstrated that regulatory CD4(+) T cells play an important direct role in the prevention of peripheral CD8(+) T cell-mediated autoimmunity.     

A homolog of Bacillus subtilis trigger factor in Listeria monocytogenes is involved in stress tolerance and bacterial virulence

Molecular chaperones play an essential role in the folding of nascent chain polypeptides, as well as in the refolding and degradation of misfolded or aggregated proteins. They also assist in protein translocation and participate in stress functions. We identified a gene, designated tig, encoding a protein homologous to trigger factor (TF), a cytosolic ribosome-associated chaperone, in the genome of Listeria monocytogenes. We constructed a chromosomal Delta tig deletion and evaluated the impact of the mutation on bacterial growth in broth under various stress conditions and on pathogenesis. The Delta tig deletion did not affect cell viability but impaired survival in the presence of heat and ethanol stresses. We also identified the ffh gene, encoding a protein homologous to the SRP54 eukaryotic component of the signal recognition particle. However, a Delta ffh deletion was not tolerated, suggesting that Ffh is essential, as it is in Bacillus subtilis and Escherichia coli. Thus, although dispensable for growth, TF is involved in the stress response of L. monocytogenes. The Delta tig mutant showed no or very modest intracellular survival defects in eukaryotic cells. However, in vivo it showed a reduced capacity to persist in the spleens and livers of infected mice, revealing that TF has a role in the pathogenicity of L. monocytogenes.     

Influence of temperature acclimation and gut content on the supercooling ability of the land snail Cornu aspersum

The invasive land snail Cornu aspersum possesses a low ability to supercool (c. -5 degrees C in winter) and survives only minimal ice formation in its body fluids, what may limit its expansion to colder environments. In the present study, we investigated the influence of acclimation and starvation on its supercooling ability. During eight weeks, individuals were maintained at 20 degrees C, fed or starved, or placed at 5 degrees C, directly or with progressive acclimation to cold and shorter photoperiod. Temperature of crystallisation of whole individual (Tc(I)) and hemolymph (Tc(H)), mass data and gut content were recorded every two weeks. Hemolymphatic glucose and glycerol were measured at the end of experiment and occurrence of intestinal ice-nucleating agents (INA) was researched. Acclimation had no effect on Tc(I) but stimulated purging of the gut. Starvation induced a slight decrease of Tc(I) whereas a high quantity of alimentary particles in the digestive tract limited the supercooling ability. Glucose and glycerol were not synthesized in cold conditions. Mean Tc(H) was low (c. -17 degrees C), some INA being present in hemolymph of fed animals. Intestinal content of starved individuals exhibited a mean Tc of c. -6 degrees C, decreasing to c. -12 degrees after heating, suggesting the presence of organic INA.     

Choreoathetosis – an unusual adverse effect of dihydroartemisinin-piperaquine: a case report

Background

Dihydroartemisinin-piperaquine is a combination of dihydroartemisinin and piperaquine which is highly effective in the treatment of uncomplicated falciparum malaria. Its adverse effects are generally tolerable and temporary. Choreoathetosis, an involuntary movement disorder characterized by continuous irregular twisting of the body, is not a documented adverse effect of this medication.

Case presentation

A 41-year-old Cameroonian man of black African ethnicity was brought to our primary care hospital because over the previous 6 hours he had been experiencing involuntary twisting movements of his body and he no longer had control of his limbs. Earlier that day, he had been prescribed an appropriate dose of dihydroartemisinin-piperaquine in our hospital. The abnormal movements started approximately 3 hours after ingesting the first dose of the drug. The review of systems and his past history were unremarkable. On clinical examination, he was conscious and oriented but was unsteady and displayed continuous generalized irregular twisting movements combined with abrupt low amplitude flinging of his limbs. Dihydroartemisinin-piperaquine-induced generalized choreoathetosis was diagnosed. He was sedated with diazepam and dihydroartemisinin-piperaquine was discontinued. The antimalarial drug was substituted with artemether-lumefantrine combination. The clinical progress was good and he was discharged home after 72 hours. No further abnormalities were noted during 7 months of follow-up.

Conclusion

Although dihydroartemisinin-piperaquine is increasingly popular as a well-tolerated/efficacious antimalarial drug, clinicians must note the rare possibility of choreoathetosis as an adverse effect of this medication and educate patients accordingly.

     

Lack of Cross-Resistance to Cry19A from Bacillus thuringiensis subsp. jegathesan in Culex quinquefasciatus (Diptera: Culicidae) Resistant to Cry Toxins from Bacillus thuringiensis subsp. israelensis

Culex quinquefasciatus mosquitoes with high levels of resistance to single or multiple toxins from Bacillus thuringiensis subsp. israelensis were tested for cross-resistance to the Bacillus thuringiensis subsp. jegathesan polypeptide Cry19A. No cross-resistance was detected in mosquitoes that had been selected with the Cry11A, Cry4A and Cry4B, or Cry4A, Cry4B, Cry11A, and CytA toxins. A low but statistically significant level of cross-resistance, three to fourfold, was detected in the colony selected with Cry4A, Cry4B, and Cry11A. This cross-resistance was similar to that previously detected with B. thuringiensis subsp. jegathesan in the same colony. These data help explain the toxicity of B. thuringiensis subsp. jegathesan against the resistant colonies and indicate that the Cry19A polypeptide might be useful in managing resistance and/or as a component of synthetic combinations of mosquitocidal toxins.     

Role of the envelope genetic context in the development of enfuvirtide resistance in human immunodeficiency virus type 1-infected patients

Acquired human immunodeficiency virus type 1(HIV-1) resistance to the fusion inhibitor enfuvirtide (ENF) is primarily associated with mutations within the highly conserved first heptad repeat (HR1) region of gp41. Viral env sequences, however, are remarkably variable, and the envelope genetic background could have an important impact on optimal expression of HR1 mutations. We have examined the genetic evolution of env sequences, ENF susceptibility, and Env replicative capacity in patients failing ENF treatment. Sequential plasma-derived virus populations, obtained from six patients initiating ENF treatment as part of a salvage therapy, were studied using a recombinant phenotypic assay evaluating the entire gp120 and the gp41 ectodomains. Regardless of major differences in the baseline ENF susceptibilities, viral populations with similar phenotypic ENF resistance (50% inhibitory concentration, >3,000 ng/ml) were selected under treatment in four of six patients. As expected, in all patients ENF-resistant viruses harbored one or more HR1 mutations (positions 36, 38, and 43). Interestingly, in five patients the emergence of resistance mutations was not associated with reduced Env replicative capacity. Phylogenetic analysis of env sequences in sequential samples from two patients showed that the HR1 mutations had emerged in the context of env quasi-species that were different from those prevalent at baseline. Thus, the envelope genetic context appears to play a critical role in the selection of HR1 mutations and the expression of ENF resistance, thereby conditioning the evolution of HIV-1 under fusion inhibitor selective pressure.