Patients’ Mental Health Journeys: A Qualitative Case Study with Interactive Computer-Assisted Client Assessment Survey (iCASS)

Despite growing concerns about common mental disorders (CMDs), challenges persist in accessing timely and appropriate care, especially for immigrant, refugee, racialized and low-income groups. Partnering with a community health centre serving these populations in Toronto, we examined the Interactive Computer-assisted Client Assessment Survey (iCCAS) that screens for CMDs (depression, generalized anxiety, post-traumatic stress, and alcohol overuse) and related social factors. In this case study design with embedded units, we explored the mental health care journeys of patients who screened positive for a CMD. The analysis identified three major pathways of care: (1) early detection of previously unidentified CMDs; (2) detection of comorbid mental health conditions; and (3) prevention of possible relapse and/or management of existing previously recognized mental health condition. These cases indicate iCCAS holds potential to facilitate more open, tailored, and informed collaborations between patients and clinicians regarding mental health care plans.     

Plasma levels of Rifampicin and Pyrazinamide with pre and post meal administration in tuberculosis patients

Context

Various factors affect plasma concentrations of antitubercular drugs in different populations so dosing schedule should be adjusted after therapeutic drug monitoring.

Influence of acyl chain length on transfection mediated by acylated PEI nanoparticles

Polyethylenimine (750 kDa) has been derivatized to influence the proton sponge mechanism and hydrophobic-hydrophilic balance. The polymer was acylated using acid anhydrides of varying carbon chain length, followed by cross-linking with PEG-bis-P to form compact nanoparticles. The chemical linkages in the particles were characterized by FTIR and NMR spectroscopy. The hydrodynamic diameter of nanoparticles was found to be in the range of 83.5-124 nm. AFM imaging of native and DNA-loaded nanoparticles revealed highly compact and spherical shape. The positive surface charge on particles decreased with the increase in percentage of acylation and also on complexing with DNA. The buffering capacity of PEI was reduced considerably on preparing acylated nanoparticles. The nanoparticles formed stable complexes with DNA and higher weight ratios were required for formation of electro-neutral complexes. Further, these nanoparticles were investigated for their gene delivery efficacy on COS-1 cells. It was found that acylated PEI nanoparticles were 5-12-fold more efficient transfecting agents as compared to native PEI (750 kDa) and commercially available transfecting agent lipofectin. The MTT colorimetric assay revealed of considerable reduction in toxicity of acylated PEI nanoparticles as compared PEI. Of all the systems prepared, nanoparticles with 30% acylation using propionic anhydride were found to be the most efficient in in vitro transfection.     

Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium

Regulation and dysregulation of intracellular calcium (Ca2+) signaling via the inositol 1,4,5-trisphosphate receptor (InsP3R) has been linked to many cellular processes and pathological conditions. In the present study, addition of neuronal calcium sensor-1 (NCS-1), a high-affinity, low-capacity, calcium-binding protein, to purified InsP3R type 1 (InsP3R1) increased the channel activity in both a calcium-dependent and -independent manner. In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway. To determine whether InsP3R1/NCS-1 interaction could be functionally relevant in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithium, a salt widely used for treatment of bipolar disorders. Lithium inhibited the enhancing effect of NCS-1 on InsP3R1 function, suggesting that InsP3R1/NCS-1 interaction is an essential component of the pathomechanism of bipolar disorder.     

Cinnamic acid, from the bark of Cinnamomum cassia, regulates glucose transport via activation of GLUT4 on L6 myotubes in a phosphatidylinositol 3-kinase-independent manner

Background: Cinnamomum cassia (Family: Lauraceae) is an Ayurvedic medicinal plant used traditionally for the treatment of a number of diseases, including diabetes. The hypoglycemic effect of this plant has been established in vivo. However, the effects of cinnamic acid, isolated from C. cassia, on the insulin signaling cascade in an in vitro model have not been elucidated. Hence, the aim of the present study was to evaluate the anti‐diabetic effect of cinnamic acid on glucose transport by L6 myotubes. Methods:  The mechanism of action of cinnamic acid was determined using specific targets in the insulin signaling pathway, including protein tyrosine phosphatase (PTP) 1B, phosphatidylinositol 3‐kinase (PI3‐K) and the glucose transporter GLUT4. After differentiation of myoblast to myotubes, the cells were serum deprived for 5 h and then treated with 1 ng/mL cinnamic acid and 50 μmol/L rosiglitazone for 18 h and 100 nmol/L insulin for 20 min for gene expression studies. Results:  Expression of GLUT4 mRNA was increased following treatment of L6 myotubes with 1 ng/mL cinnamic acid. Furthermore, cinnamic acid inhibited PTP1B activity (by 96.5%), but had no significant effect on PI3‐K activity. Conclusion:  On the basis of the results of the present study, we postulate that cinnamic acid isolated from the hydro‐alcoholic extract of Cinnamomum cassia activates glucose transport by a PI3‐K‐independent pathway. However, the detailed mechanism of action requires further analysis.     

Effect of nasal immunization with protective antigen of Bacillus anthracis on protective immune response against anthrax toxin

Anthrax toxin consists of three proteins: protective antigen (PA), lethal factor (LF) and edema factor (EF). PA in combination with LF (lethal toxin) is lethal to mammalian cells and is the major component of human anthrax vaccine. Immunization with PA elicits the production of neutralizing antibodies that form a major component of the protective immunity against anthrax. Recent reports have shown that neutralizing antibody titres can serve as a reliable surrogate marker for protection against anthrax. In the present study, the use of non-invasive routes such as bare skin and nose for immunization with PA on its protective immune response was investigated. Mice were inoculated intranasally (i.n.), subcutaneously (s.c.) or through the skin on days 0, 15 and 28 with purified PA. Intranasal and subcutaneous immunization with PA resulted in high IgG ELISA titers. The predominant subclass in each group was IgG1. High titres of IgA were observed only in i.n. immunized mice. In a cytotoxicity assay these sera protected J774A.1 cells from lethal toxin challenge. The results suggest that non-invasive nasal immunization may be useful in improving vaccination strategies against anthrax.     

Neutrophil-to-lymphocyte ratio is a novel predictor of venous thrombosis in polycythemia vera

We investigated the neutrophil-to-lymphocyte ratio (NLR) as a predictor of thrombosis in polycythemia vera (PV). After a median follow-up of 2.51 years, of 1508 PV patients enrolled in the ECLAP study, 82 and 84 developed arterial and venous thrombosis, respectively. Absolute counts of total leukocytes, neutrophils, lymphocytes, platelets, and the NLR were tested by generalized additive models (GAM) to evaluate their trend in continuous scale of thrombotic risk. Only for venous thrombosis, we showed that baseline absolute neutrophil and lymphocyte counts were on average respectively higher (median: 6.8 × 10⁹/L, p = 0.002) and lower (median: 1.4 × 10⁹/L, p = 0.001), leading to increased NLR values (median: 5.1, p = 0.002). In multivariate analysis, the risk of venous thrombosis was independently associated with previous venous events (HR = 5.48, p ≤ 0.001) and NLR values ≥5 (HR = 2.13, p = 0.001). Moreover, the relative risk in both low- and high-standard risk groups was almost doubled in the presence of NLR ≥ 5. These findings were validated in two Italian independent external cohorts (Florence, n = 282 and Rome, n = 175) of contemporary PV patients. Our data support recent experimental work that venous thrombosis is controlled by innate immune cells and highlight that NLR is an inexpensive and easily accessible prognostic biomarker of venous thrombosis.Subject terms: Myeloproliferative disease, Risk factors