Impact of Meal Context On Food Advertising Outcomes

This research examines to what extent the presence of meal context as a visual component embedded in food advertisements influences consumers’ responses. It empirically tested whether meal context (vs. no meal context) impacts consumers’ attitude towards the advertisement, the advertised brand, brand purchase intentions, product evaluation and appetitive motivation. An experiment involving a range of existing food products and brands was conducted with a sample of adult Canadian consumers. Contrary to predictions, meal context did not significantly impact consumer responses. Brand familiarity and product preference emerged as the most important predictors of consumer responses. This research has a number of implications for future research on meal context effects

Vitamin D and Alzheimer’s Disease: Neurocognition to Therapeutics

Alzheimer’s disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Design, Synthesis and Biological Evaluation of Small Molecule Inhibitors of the Hedgehog Signaling Pathway

The Hedgehog (Hh) signaling is an important embryonic developmental pathway normally responsible for tissue growth, differentiation and patterning. However, aberrant activity of this signaling cascade has been implicated in several types of cancer. Therefore, inhibition of the dysregulated pathway is a promising therapeutic target for treating Hh-dependent malignancies such as basal cell carcinoma (BCC) and medulloblastoma (MB). Previous studies resulted in the FDA approval of Vismodegib, a small molecule inhibitor of the Hh pathway, for the treatment of advanced BCC. Similarly, several other small molecule Hh antagonists have progressed into clinical trials. Moreover, several components within the Hh pathway have proven to be druggable in ‘proof-of-concept’ studies. Nonetheless, several challenges in the discovery and development process for small molecules targeting this pathway have been noted. For instance, multiple mechanisms of resistance to Hh inhibitors have been identified. This has prompted extensive search for novel inhibitors that function via mechanisms that will retain activity in the presence of pathway signaling resistant to current therapy. Consequently, a ligand based approach was undertaken to develop Hh inhibitors based on two distinct lead structures namely Vitamin D3 (VD3) and Itraconazole (ITZ). An interdisciplinary approach utilizing synthetic organic chemistry transformations and molecular biology techniques was adopted to study the Hh inhibitory effects of probing relevant biological systems with aforementioned small molecule modulators and their derivatives. Information thus obtained guided the design of improved second-generation Hh inhibitors. A structure-activity-relationship study to identify the Hh inhibitory pharmacophore of VD3 was pursued. Based on the findings, VD3 based anti-Hhanalogues with improved potency and selectivity were designed, synthesized and evaluated. Next, a synthetic methodology for preparing ITZ derivatives with stereochemically defined hydroxylated side chains was optimized. Preliminary evaluation of resultant hybrid ITZ analogues obtained via this synthetic route identified Hh inhibitors demonstrating nanomolar potencies. Taken together, the preliminary identification of several improved Hh inhibitory scaffolds through these studies will facilitate further comprehensive biological evaluation of the promising derivatives

Photolysis of 5-Azido-3-Phenylisoxazole at Cryogenic Temperature: Formation and Direct Detection of a Nitrosoalkene

To enhance the versatility of organic azides in organic synthesis, a better understanding of their photochemistry is required. Herein, the photoreactivity of azidoisoxazole 1 was characterized in cryogenic matrices with IR and UV-Vis absorption spectroscopy. The irradiation (λ = 254 nm) of azidoisoxazole 1 in an argon matrix at 13 K and in glassy 2-methyltetrahydrofuran (mTHF) at 77 K yielded nitrosoalkene 3. Density functional theory (DFT) and complete active space self-consistent field (CASSCF) calculations were used to aid the characterization of nitrosoalkene 3 and to support the proposed mechanism for its formation. It is likely that nitrosoalkene 3 is formed from the singlet excited state of azidoisoxazole 1 via a concerted mechanism or from cleavage of an intermediate singlet nitrene that does not undergo efficient intersystem crossing to its triplet configuration

Overexpression of GRP78 receptor and its Chemical Biology in Cancer and Autoimmune Diseases: High risk for COVID 19?

ACE2 receptor has been the focus of scientific community as receptor of COVID 19 and is been explored for therapeutic targeting. Recently, another receptor for COVID 19 was reported, the Glucose Regulated Protein 78 (GRP78). GRP78, a heat shock protein is an endoplasmic reticulum (ER) stress response protein. In cancer and certain autoimmune diseases there are reports of upregulation of GRP78. In breast cancer, prostate cancer, melanomas and malignant gliomas GRP78 overexpresses. Chemoresistance has been linked to upregulated GRP78. So, cancer patients might be at increased risk of COVID 19 infection owing to receptor abundance. We propose that tumour associated endothelial cells having upregulated GRP78 might also participate in dissemination of the virus. GRP78 also gets upregulated in rheumatoid arthritis and inflammatory bowel disease (IBD). Thus, both cancer patients as well as autoimmune diseases (Rheumatoid arthritis and IBD) should be considered as high-risk groups for COVID 19

Identification of Vitamin D3-Based Hedgehog Pathway Inhibitors That Incorporate an Aromatic A‑Ring Isostere

Previous structure–activity relationship studies for vitamin D3 (VD3) inhibition of Hedgehog (Hh) signaling directed the design, synthesis, and evaluation of a series of VD3-based analogues that contain an aromatic A-ring mimic. Characterization of these compounds in a series of cellular assays demonstrated their ability to potently and selectively down-regulate Hh pathway signaling. The most active of these, <b>17</b>, inhibited pathway signaling in Hh-dependent mouse fibroblasts (IC₅₀ = 0.74 ± 0.1 μM) and cultured cancer cells (IC₅₀ values 3.8 ± 0.1 to 5.2 ± 0.2 μM). In addition, <b>17</b> demonstrated reduced activation of the vitamin D receptor (VDR) compared to VD3 in these cellular models. These results suggest that VD3-based analogues with an aromatic A-ring are a valid scaffold for the development of more selective and potent Hh pathway inhibitors and identify <b>17</b> as an intriguing lead from this class of compounds for further development. In addition, our analysis of Hh pathway inhibitors in cancer cells suggests that the murine basal cell carcinoma cell line ASZ001 and the human medulloblastoma cell line DAOY are appropriate in vitro cancer models for early stage evaluation of pathway inhibition

Vitamin D and Alzheimer’s Disease: Neurocognition to Therapeutics

Alzheimer’s disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene-environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients

Vitamin D and immuno-pathology of COVID-19: many interactions but uncertain therapeutic benefits

Introduction: COVID-19 pandemic has caused huge loss of human lives and extensive socio-economic damages. The immuno-pathology of this disease is neither clearly understood, nor there are effective drugs for severe cases of COVID-19. Repurposing of available drugs for the treatment of COVID-19 is imperative. Areas Covered: This review has gathered the evidence from PubMed, Google Scholar, WHO, and other reliable websites on COVID-19 and summarized the existing knowledge of the immuno-pathology of COVID-19. We elucidated how vitamin D through its diverse actions on immune effector cells, epithelial cells, or rennin-angiotensin-aldosterone system could have a modulatory role on the pathogenic mechanisms of COVID-19. The epidemiological evidence associating vitamin D deficiency with the severity and incidence of COVID-19 is also presented. However, the evidence of clinical benefit to patients of COVID-19 from randomized controlled trials with vitamin D has not come as yet. Expert opinion: It is now established that fatality of COVID-19 is primarily determined by hyperactivation of the host's innate immune system in response to SARS-CoV-2 invasion, and thus the research on the immuno-modulatory and other roles of vitamin D against viral infections should be pursued vigorously. This would be also useful for future pandemics caused by other novel viruses