Design and Development of Acetylthiocholine Electrochemical Biosensor Based on Zinc Oxide–Cerium Oxide Nanohybrid Modified Platinum Electrode

Acetylcholinesterase (AChE) enzyme has been predominantly used for the detection of pesticides and metal ions. But, these sensors respond to pesticides as well as metal ions at certain concentration, which results in poor selectivity. Hence in this work, the amount of thiocholine produced during AChE inhibition has been estimated to detect the residual activity of AChE enzyme in-turn to enhance the efficiency of the biosensor. In this context, Pt/ZnO–CeO₂/AChE/Chitosan based biosensor has been developed for sensitive voltammetric quantification of thiocholine in AChE. The sensor exhibited enhanced electron transfer rate, good conductivity and biocompatibility. Both the intrinsic and extrinsic parameters were simultaneously optimized using second order polynomial regression to get the best conditions for ATCh determination. Under optimized experimental conditions, the redox peak current was linear over the concentration range of 0.1–1.5 mM with detection and quantification limit of 0.05 and 0.15 μM respectively and the sensitivity of 1.47 μA mM^?1.     

Toll-like receptors: Significance,ligands, signaling pathways,and functions in mammals

This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity. Interestingly, they also have a significant role in immunotherapy and vaccination. Signals generated by TLRs are transduced through NFκB signaling and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory molecules, which promote inflammatory responses. The excess production of these cytokines leads to grave systemic disorders like tumor growth and autoimmune disorders. Hence, regulation of the TLR signaling pathway is necessary to keep the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFκB, and TRAF3 are involved in modulating the TLR pathways to induce appropriate response. Though quantification of these TLRs helps in correlating the magnitude of immune response exhibited by the animal, there are several internal, external, genetic and animal factors that affect their expression patterns. So it can be concluded that any identification based on those expression profiles may lead to improper diagnosis during certain conditions.     

Migrating foreign body into the common carotid artery and internal jugular vein – A rare case

Ingested foreign bodies are a fairly common otorhinolaryngological emergencies encountered in Malaysia. The vast majority of these foreign bodies are fish bones which most commonly are impacted at the level of the cricopharynx. Rarely, however, a foreign body may migrate extraluminally and may even extrude subcutaneously. We report a rare occurrence where a fish bone not only migrated extraluminally, it was found to have migrated into the common carotid artery and the internal jugular vein and required surgical removal.     

The effects of preexisting depression on cerebrovascular health outcomes in geriatric continuing care

BACKGROUND: Previous studies have investigated depression as the cause and outcome of vascular deficit in elderly persons. METHODS: The authors wanted to determine whether baseline depression is predictive of subsequent cardiovascular events in very elderly persons residing in a continuing care retirement community (n = 181). RESULTS: Controlling for demographic factors, both depression and the number of cardiovascular risk factors (CVRFs) at baseline were strongly predictive of stroke, whereas only CVRFs strongly predicted myocardial infarctions. Depression accounted for 12% of the variance in stroke incidence, beyond the contribution of CVRFs. Path analysis indicated that depression was also a partial moderator of the effect of CVRFs. CONCLUSIONS: In support of the vascular depression hypothesis, the study findings indicate that, for the oldest old, depression may be a strong predictor of future stroke. The presence of depression in elderly patients should alert physicians to carefully investigate other stroke risk factors and to integrate depression into an overall intervention regimen for reducing patients' risks for stroke.     

Effects of Q/N-rich, polyQ, and non-polyQ amyloids on the de novo formation of the [PSI+] prion in yeast and aggregation of Sup35 in vitro

Prions are infectious protein conformations that are generally ordered protein aggregates. In the absence of prions, newly synthesized molecules of these same proteins usually maintain a conventional soluble conformation. However, prions occasionally arise even without a homologous prion template. The conformational switch that results in the de novo appearance of yeast prions with glutamine/aspargine (Q/N)-rich prion domains (e.g., [PSI+]), is promoted by heterologous prions with a similar domain (e.g., [RNQ+], also known as [PIN+]), or by overexpression of proteins with prion-like Q-, N-, or Q/N-rich domains. This finding led to the hypothesis that aggregates of heterologous proteins provide an imperfect template on which the new prion is seeded. Indeed, we show that newly forming Sup35 and preexisting Rnq1 aggregates always colocalize when [PSI+] appearance is facilitated by the [RNQ+] prion, and that Rnq1 fibers enhance the in vitro formation of fibers by the prion domain of Sup35 (NM). The proteins do not however form mixed, interdigitated aggregates. We also demonstrate that aggregating variants of the polyQ-containing domain of huntingtin promote the de novo conversion of Sup35 into [PSI+]; whereas nonaggregating variants of huntingtin and aggregates of non-polyQ amyloidogenic proteins, transthyretin, alpha-synuclein, and synphilin do not. Furthermore, transthyretin and alpha-synuclein amyloids do not facilitate NM aggregation in vitro, even though in [PSI+] cells NM and transthyretin aggregates also occasionally colocalize. Our data, especially the in vitro reproduction of the highly specific heterologous seeding effect, provide strong support for the hypothesis of cross-seeding in the spontaneous initiation of prion states.     

Clinical presentation and diagnostic sensitivity of laboratory tests for Strongyloides stercoralis in travellers compared with immigrants in a non-endemic country

OBJECTIVES: To assess whether the clinical and laboratory methods for diagnosing Strongyloides stercoralis infection in non-endemic countries is different between those who are chronically exposed and those who travel. METHODS: Analysis of laboratory and clinical data from 204 patients having S. stercoralis infection at the Hospital for Tropical Diseases, London. RESULTS: Sixty-four travellers and 128 immigrants from endemic countries had laboratory-proven strongyloides. In those with microscopically proven disease, serology was 73% sensitive in travellers and 98% sensitive in immigrants (P < 0.001). There was no difference in the eosinophil count between the two groups with 19% having a normal count. Patterns of symptoms varied between the groups, and around one-third were asymptomatic in both groups. Serology was of limited use in follow-up. CONCLUSIONS: Eosinophil count and stool microscopy are insufficiently sensitive to be used alone for screening strongyloides. The sensitivity of serology is good in immigrants with chronic infection, but lower in travellers.     

The effectiveness of pharmaceutical interventions for obesity: weight loss with orlistat and sibutramine in a United Kingdom population-based cohort

Aims

Drug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care.

Methods

We used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95% confidence intervals (CI) was estimated.

Results

We identified 100 701 patients receiving orlistat, 15 355 receiving sibutramine and 508 140 non-intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m⁻², respectively. Patients receiving orlistat lost, on average, 0.94 kg month⁻¹ (0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month⁻¹ (1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non-intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month⁻¹.

Conclusions

Orlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials.