Evolutionary puzzle of Toxoplasma gondii with suicidal ideation and suicide attempts: An updated systematic review and meta‐analysis

The World Health Organization has reported an annual global suicide rate of 14.5 per 100,000 people. On the other hand, it is estimated that approximately one‐third of the global population are infected with Toxoplasma gondii (T. gondii) parasite. It is widely assumed that microbial pathogens, such as T. gondii, are probably associated with affective and behavioural modulation. The present article aimed to assess the proposed role of toxoplasmosis in raising the risk of suicidal ideation (SI) and suicide attempts (SA) using the available epidemiological data. Seven major electronic databases and the Internet search engine Google were searched for all the studies published between the 1st of January 1950 and 31st of October 2019. The heterogeneity and the risk of bias within and across studies were assessed. Following data extraction, pooled odds ratios (ORs) with 95% confidence interval (CI) across studies were calculated using the random‐effects models. A total number of 9,696 articles were screened and 27 studies were regarded as eligible in our systematic review (SI with five papers and 22 papers on SA). A significant association was detected between antibodies against T. gondii with TA (ORs = 1.57; 95% confidence interval [CI] 1.23–2.00, p = .000). Exploration of the association between T. gondii and SA yielded a positive effect of seropositivity for IgG antibodies but not IgM. Despite the limited number of studies, a statistical association was detected between suicidal behaviours and infection with latent T. gondii.     

Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty

Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.     

Small Conductance Ca2+-Activated K+ Channels Formed by the Expression of Rat SK1 and SK2 Genes in HEK 293 Cells

The rat SK1 gene ( rSK1 ) does not form functional Ca²⁺-activated potassium channels when expressed alone in mammalian cell lines. Using a selective antibody to the rSK1 subunit and a yellow fluorescent protein (YFP) tag we have discovered that rSK1 expression produces protein that remains largely at intracellular locations. We tested the idea that rSK1 may need an expression partner, rSK2, in order to form functional channels. When rSK1 was co-expressed with rSK2 in HEK 293 cells it increased the current magnitude by 77 ± 34 % (as compared with cells expressing rSK2 alone). Co-expression of rSK1 with rSK2 also changed the channel pharmacology. The sensitivity of SK current to block by apamin was reduced ~16-fold from an IC₅₀ of 94 p m (for SK2 alone) to 1.4 n m (for SK2 and SK1 together). The sensitivity to block by UCL 1848 (a potent small molecule blocker of SK channels) was similarly reduced, ~26-fold, from an IC₅₀ of 110 p m to 2.9 n m . These data clearly demonstrate that rSK1 and rSK2 subunits interact. The most likely explanation for this is that the subunits are able to form heteromeric assemblies.     

Role of endotoxemia in cardiovascular dysfunction and lethality: virulent and nonvirulent Escherichia coli challenges in a canine model of septic shock.

We investigated whether the severity of septic shock is determined by virulence factors associated with or the levels of endotoxemia produced by two Escherichia coli strains. Canines were challenged intraperitoneally with an E. coli strain (O6:H1:K2) that has virulence factors associated with human disease or with an equal dose of a nonvirulent strain (O86:H8) that lacks these factors. Both strains were administered in viable, heat-killed, and purified endotoxin forms. Median survival times with the virulent strain compared with the nonvirulent strain were shorter with viable bacteria (5 x 10(10) CFU/kg) (144 h versus > 672 h; Wilcoxon, P = 0.03), longer with heat-killed bacteria (5 x 10(9) CFU/kg) ( > 676 h versus 26 h; P = 0.03), and similar with purified endotoxin (15 mg/kg) (28 h versus 48 h; P = 0.71). However, whether the challenge contained viable bacteria, heat-killed bacteria, or purified endotoxin, the virulent strain produced less endotoxemia (P = 0.001). Hence, the changing outcomes with differing forms of the two strains cannot be attributed solely to endotoxin levels. The viable virulent strain caused less endotoxemia but more harm, and this does not appear to be explained by a more potent endotoxin or other heat-stable component. This study suggests that circulating endotoxin levels per se are less important in the outcome of septic shock than virulence factors associated with E. coli strains. Furthermore, the data call into question the significance of the endotoxin concentration in the blood in predicting the severity of shock and the lethality of gram-negative infections.     

Comparison of automated and manual methods for urinalysis

The authors compared results for accuracy and precision obtained by a semiautomated prototype International Remote Imaging Systems, Inc. (IRIS) urinalysis workstation (IUW) with those from quantitative manual urinalysis (QMU). Three technologists skilled in urinalysis each performed 172 urinalyses with both the IUW and QMU methods. The results show that the IUW method is likely to yield comparable counts for particulate analytes compared with the QMU, except for casts. The QMU reported significantly (P less than 0.001) more casts than the IUW method. This difference is related to at least a ninefold greater volume of untreated urine examined by the QMU method than the IUW method. The IUW method may provide a more accurate result than the QMU method at very low and high concentrations of particulate analytes. The result from 24 blind duplicate urines also analyzed by each of the three technologists with both methods showed comparable precision for particulate analytes between the two methods except for red blood cells; the QMU method had significantly (P less than 0.001) better precision for this analyte.     

What is the appropriate aganglionic bowel length on contrast enema for attempting single stage transanal endorectal pull-through in Hirschsprung disease?

PurposeTo identify influence of different values of age and abnormal bowel length in HD patients selected for single stage TERPT which affects the technique of surgery.MethodsThis observational study was carried out for over 2.5 years. All children younger than 14 years old with clinical suspicion for HD, typical transitional zone (TZ) on contrast enema (CE) distal to splenic flexure, preoperative diagnosis approved by full thickness biopsy, no previous surgical history and no urgency were included. The distance between the anus and TZ was considered as aganglionic length on CE. Biopsy was taken from distal to proximal of resected bowel to reach circumferentially normal innervated bowel. Paired sample Student's t-test, Pearson correlation test, receiver operating characteristic (ROC) analysis were performed.ResultsForty-eight patients were enrolled in this study. Measured mean for aganglionic bowel length on CE and pathology were 33.5 ± 17.1 cm and 56.8 ± 33.5 cm, respectively (p < 0.01). Correlation coefficient (R) and coefficient of determination (R2) were 0.632 and 40%, respectively (p < 0.01). The difference between radiologic and pathologic measurements in females was higher than males (mean: 29.3 vs 21.9 cm) but was not statistically significant (p = 0.75). There was statistically significant difference between CE and pathologic results in the infants younger than 10 months (p = .004). Abnormal bowel length equal to 52 cm predicted requirement of laparoscopy assistance/laparotomy with 75% sensitivity and 85% specificity.ConclusionOur investigation showed it is safe to attempt for single stage TERPT when aganglionic length on CE is less than 52 cm and the child with HD is older than 10 months. Chance of requiring additional laparotomy or laparoscopy assistance is low in these patients.Type of studyStudy of diagnostic test.Level of evidenceLevel II.     

Mechanical lengthening of porcine small intestine with decreased forces

Introductionshort bowel syndrome is marked by inadequate intestinal surface area to absorb nutrients. Current treatments are focused on medical management and surgical reconfiguration of the dilated intestine. We propose the use of spring-mediated distraction enterogenesis as a novel intervention to increase intestinal length. Given our previous success lengthening intestinal segments using springs with spring constant ~7 N/m that exerts 0.46 N or higher, we sought to determine the minimal force needed to lengthen porcine small intestinal segments, and to explore effects on intestine over time.MethodsJuvenile Yucatan pigs underwent laparotomy with enterotomy to introduce nitinol springs intraluminally (n = 21 springs). Bowel segments (control, spring-distracted) were retrieved on post-operative day (POD) 7 and 14, and lengths measured. Thickness of cross-sectional intestinal layers were measured using H&E, and submucosal collagen fiber orientation measured using trichrome stained sections.Resultsall pigs survived to POD7 and 14. Spring constants of at least 2 N/m exerting a minimum force of 0.10 N significantly lengthened intestinal segments (p <0.0001). The stronger the spring force, the greater the induced thickness of various intestinal layers at POD7 and 14. Collagen fiber orientation was also more disordered because of stronger springs.Conclusiona spring constant of approximately 2 N/m exerting 0.10 N and greater significantly lengthens intestinal segments and stimulates intestinal structural changes at POD7 and 14. This suggests a decreased force is capable of inducing spring-mediated distraction enterogenesis.     

A randomized,double-blind placebo-controlled add-on trial to assess the efficacy,safety, and anti-atherogenic effect of spirulina platensis in patients with inadequately controlled type 2 diabetes mellitus

The efficacy of spirulina platensis (S. platensis) as an add-on therapy to metformin and its effect on atherogenic keys in patients with uncontrolled Type 2 Diabetes Mellitus (T2DM) was evaluated. Sixty patients were randomly assigned to S. platensis (2 g/day) or placebo group for three months while continuing metformin as their usual treatment. The efficacy of S. platensis was determined using the pre- and post-intervention HbA1c levels (primary outcome) as well as tracking FBS and lipid profiles levels (TC, LDL-C, TG, and HDL-C) as secondary outcomes at the different treatment time points (0,30,60,90 days). During the three–month intervention period, supplementation with S. platensis resulted in a significant lowering of HbA1c (↓1.43, p < 0.001) and FBS (↓ 24.94 mg/dL, p < 001) levels. Mean TG in the intervention group was found to be significantly lower in the intervention group than in controls (p < 0.001). Total cholesterol (TC) and its fraction, LDL-C, exhibited a fall (↓41.36 mg/dL and ↓38.4 mg/dL, respectively; p < 0.001) coupled with a marginal increase in the level of HDL-C (↑3 mg/dL; p < 0.001). Add-on therapy with S. platensis was superior to metformin regarding long-term glucose regulation and controlling blood glucose levels of subjects with T2DM. Also, as a functional supplement, S. platensis has a beneficial effect on atherogenic keys (TG and HDL-C) with no adverse events.