Clinical-based Studies Research Articles

Curcumin is effective in managing oral inflammation: An in vitro study.

Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions. This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.

Clinical metabolomics characteristics of diabetic kidney disease: A meta-analysis of 1875 cases with diabetic kidney disease and 4503 controls.

Diabetic Kidney Disease (DKD), one of the major complications of diabetes, is also a major cause of end-stage renal disease. Metabolomics can provide a unique metabolic profile of the disease and thus predict or diagnose the development of the disease. Therefore, this study summarises a more comprehensive set of clinical biomarkers related to DKD to identify functional metabolites significantly associated with the development of DKD and reveal their driving mechanisms for DKD. We searched PubMed, Embase, the Cochrane Library and Web of Science databases through October 2022. A meta-analysis was conducted on untargeted or targeted metabolomics research data based on the strategy of standardized mean differences and the process of ratio of means as the effect size, respectively. We compared the changes in metabolite levels between the DKD patients and the controls and explored the source of heterogeneity through subgroup analyses, sensitivity analysis and meta-regression analysis. The 34 clinical-based metabolomics studies clarified the differential metabolites between DKD and controls, containing 4503 control subjects and 1875 patients with DKD. The results showed that a total of 60 common differential metabolites were found in both meta-analyses, of which 5 metabolites (p<0.05) were identified as essential metabolites. Compared with the control group, metabolites glycine, aconitic acid, glycolic acid and uracil decreased significantly in DKD patients; cysteine was significantly higher. This indicates that amino acid metabolism, lipid metabolism and pyrimidine metabolism in DKD patients are disordered. We have identified 5 metabolites and metabolic pathways related to DKD which can serve as biomarkers or targets for disease prevention and drug therapy.

A critical overview of challenging roles of medicinal plants in improvement of wound healing technology.

Chronic diseases often hinder the natural healing process, making wound infections a prevalent clinical concern. In severe cases, complications can arise, potentially leading to fatal outcomes. While allopathic treatments offer numerous options for wound repair and management, the enduring popularity of herbal medications may be attributed to their perceived minimal side effects. Hence, this review aims to investigate the potential of herbal remedies in efficiently treating wounds, presenting a promising alternative for consideration. A literature search was done including research, reviews, systematic literature review, meta-analysis, and clinical trials considered. Search engines such as Pubmed, Google Scholar, and Scopus were used while retrieving data. Keywords like Wound healing 'Wound healing and herbal combinations', 'Herbal wound dressing', Nanotechnology and Wound dressing were used. This review provides valuable insights into the role of natural products and technology-based formulations in the treatment of wound infections. It evaluates the use of herbal remedies as an effective approach. Various active principles from herbs, categorized as flavonoids, glycosides, saponins, and phenolic compounds, have shown effectiveness in promoting wound closure. A multitude of herbal remedies have demonstrated significant efficacy in wound management, offering an additional avenue for care. The review encompasses a total of 72 studies, involving 127 distinct herbs (excluding any common herbs shared between studies), primarily belonging to the families Asteraceae, Fabaceae, and Apiaceae. In research, rat models were predominantly utilized to assess wound healing activities. Furthermore, advancements in herbal-based formulations using nanotechnology-based wound dressing materials, such as nanofibers, nanoemulsions, nanofiber mats, polymeric fibers, and hydrogel-based microneedles, are underway. These innovations aim to enhance targeted drug delivery and expedite recovery. Several clinical-based experimental studies have already been documented, evaluating the efficacy of various natural products for wound care and management. This signifies a promising direction in the field of wound treatment. In recent years, scientists have increasingly utilized evidence-based medicine and advanced scientific techniques to validate the efficacy of herbal medicines and delve into the underlying mechanisms of their actions. However, there remains a critical need for further research to thoroughly understand how isolated chemicals extracted from herbs contribute to the healing process of intricate wounds, which may have life-threatening consequences. This ongoing research endeavor holds great promise in not only advancing our understanding but also in the development of innovative formulations that expedite the recovery process.

Gender differences in horizontal strabismus: Systematic review and meta-analysis shows no difference in prevalence, but gender bias towards females in the clinic.

Strabismus is a misalignment of the visual axis that affects 2-3% of the population and can lead to loss of binocular vision. It is currently controversial whether there is a gender difference in the most common form of visual misalignment: horizontal strabismus. Some studies claimed that more females than males have an outward deviation (exotropia), while others concluded that there is no significant gender difference. No previous work has systematically explored gender differences in horizontal strabismus or has compared the results of population-based studies with those of clinic-based studies. We conducted a systematic review and meta-analysis of studies reporting the prevalence of horizontal strabismus. We included 73 population-based studies and compared their disclosed gender population with that in 141 comparable clinical-based studies. We analysed the data according to gender, strabismus type (esotropia, exotropia), and geographic region/ethnicity. Summary statistics showed a nearly identical prevalence of horizontal strabismus (2.558% for males, 2.582% for females), esotropia (1.386% males vs. 1.377% females), and of exotropia (1.035% males vs. 1.043% females). Meta-analysis results showed that these differences between males and females were not statistically significant (odds ratio (OR) = 1.01; 95% confidence interval (CI) = 0.97-1.10), but that females were significantly more frequent (by 7.50%) in clinic-based studies than males, with 5.00% more females for esotropia, and 12.20% more females for exotropia when adjusted for the population's sex ratio. The extent of the female gender bias differed between geographic regions/societies, with Asians having the lowest bias towards females and Latin American countries having the strongest bias. Males and females have the same prevalence of horizontal strabismus, including exotropia. Females with strabismus seek health care or are brought to clinics significantly more often than males. This is an example of gender bias in health care in favour of females rather than males, apparently because parents - erroneously fearing only cosmetic consequences - are more concerned about strabismus in their daughters than their sons. Societal attitudes towards females, as well as economic factors (insurance status), appear to be relevant factors that determine the magnitude of the gender bias in horizontal strabismus.

Nanoformulations-Based Metronomic Chemotherapy: Mechanism, Challenges, Recent Advances, and Future Perspectives.

Cancer-related death is a significant health and economic burden worldwide, and some conventional chemotherapy is associated with limited effectiveness in completely curing various cancers, severe adverse effects, and destruction of healthy cells. To overcome the complications associated with conventional treatment, metronomic chemotherapy (MCT) is extensively suggested. In this review, we aim to highlight the importance of MCT over conventional chemotherapeutic approach with emphasis on nanoformulations-based MCT, their mechanism, challenges, recent advances, and future perspectives. Nanoformulations-based MCT revealed remarkable antitumor activity in both preclinical and clinical settings. For example, the metronomic scheduling of oxaliplatin-loaded nanoemulsion and polyethylene glycol-coated stealth nanoparticles incorporating paclitaxel were proven very effective in tumor-bearing mice and rats, respectively. Additionally, several clinical studies have demonstrated the benefit of MCT with acceptable tolerance. Moreover, metronomic might be a promising treatment strategy for improving cancer care in low- and middle-income nations. However, an appropriate alternative to a metronomic regimen for an individual ailment, suitable combinational delivery and scheduling, and predictive biomarkers are certain parts that remain unanswered. Further clinical-based comparative research studies are mandatory to be performed before entailing this treatment modality in clinical practice as alternative maintenance therapy or in place of transferring to therapeutic management.

Effect of The Keller Funnel Method “No Touch” on Breast Augmentation and Reconstruction: A Systematic Review

Introduction: Breast augmentation is one of the most common aesthetic surgeries. Implant contamination remains a critical problem with these surgeries resulting in acute infection as well as capsular contracture. To reduce the risk of implant contamination, the “no-touch technique” utilizing the Keller funnel© has been adopted by many surgeons. This systematic review aims to investigate the advantages of the Keller Funnel method for breast augmentation-reconstruction. Materials and Methods: A systematic review of PubMed, EMBASE, the Cochrane database, and Google Scholar was performed between years 2005 to 2021. All clinical-based, retrospective and prospective studies utilizing the Keller Funnel method for breast implant insertion were selected. Results: Six studies were identified for evaluation: 5 were retrospective cohorts and 1 was prospective trial. No randomized controlled trials were found. Outcomes reported included less rates of capsular contracture (RR:0.42; P=0.0006, %95 CI=0.25-0.69), decreased levels of contamination and implant shell trauma, shorter incision lengths (35.5+/-2.1mm), less insertion time (mean=6 s), decreased complications, and ultimately greater patient satisfaction with outcomes. Conclusion: This review suggests that the Keller Funnel is a useful method “no-touch” breast augmentation and reconstruction surgery. The Keller funnel reduces bacterial contamination and subsequent capsular contracture rate, surgical time, and incision length as well as allows for easier insertion. All of these mitigate the variables that lead to reoperation. However, our findings support recommendation of a prospective randomized controlled clinical trial with larger population size and follow-up intervals.

A Comparative Finite Element Analysis of ‘Hexa-Zygomatic’ Implants vs Conventional Quad Zygomatic Implants for The Rehabilitation of Bilateral Maxillectomy Defects

Restoration of bilateral maxillectomy defects is inherently challenging. Zygomatic implants are one of the non-bone grafting solutions for restoration of such defects which require minimum armamentarium and are widely available. The Quad Zygomatic Implants have a long track record in maxillectomy defects secondary to cancer ablative surgeries. In the current scenario, they are being used in COVID associated mucormycosis maxillectomy defects. Since there is a paucity in literature on the use of zygomatic implants in the above-mentioned malady, we have used finite element analysis to assess the longevity of the Quad Zygomatic Implants concept and the newer Hexa Zygomatic Implants concept for these types of cases. The finite element analysis showed similar results for both the concepts on simulation which leads to the conclusion whereas both are viable treatment modalities. The Quad Zygomatic Implants concept is the more economically favourable and practical solution. As this a finite element analysis study, clinical based studies with long follow-up may shed light on a more conclusive clinical outcomes.

Herbal Medicine for the Management of Laxative Activity.

Constipation is one of the most common and prevalent chronic gastrointestinal conditions across the globe that is treated or managed through various methods. Laxatives are used for the treatment or management of chronic/acute constipation. But due to the adverse effects associated with these laxatives, herbal foods should be considered as alternative therapies for constipation. In this review, the laxative potential of plant-based medicines used for constipation is discussed. Constipation may be caused by various factors such as lifestyle, particular food habits, pregnancy and even due to some medication. Chronic constipation is responsible for different health issues. Pharmacological and non-pharmacological paradigms are applied for the treatment or management of constipation. In the pharmacological way of treatment, medicinal plants have a key role because of their fibrous nature. Numerous plants such as Prunus persica (Rosaceae), Cyamopsis tetragonolobus (Leguminosae), Citrus sinensis (Rutaceae), Planta goovata (Plantaginaceae), Rheum emodi (Polygonaceae), Cassia auriculata (Caesalpinacea), Ricinus communis (Euphorbiaceae), Croton tiglium (Euphorbiaceae), Aloe barbadensis (Liliaceae), Mareya micrantha (Euphorbiaceae), Euphorbia thymifolia (Euphorbiaceae), Cascara sagrada (Rhamnaceae), Cassia angustifolia (Fabaceae) have laxative activity. Medicinal plants possess a significant laxative potential and support their folklore; therefore, further, well-designed clinical-based studies are required to prove and improve the efficacy of herbal medicine for constipation. The present review showed that herbs laxative effect in various in vivo/ in vitro models.

Nutrient Composition, Antioxidant Activities and Anti-Inflammatory Effect of Jujube Fruit

Jujube (Ziziphus jujuba) fruit belongs to the Rhamnaceous family and is widely located in the tropical and subtropical regions of Asia as well as in the Mediterranean regions including Jordan. Therefore, the aim of this review was to illustrate the nutritional value of jujube fruit and its importance in human health protection as antioxidant and anti-inflammatory agent. Recently, several scientific reports have been carried out about the presence of many biologically active compounds from Z. jujuba, which may have high potential benefit in human nutrition, health, and disease. Based on previous studies, jujube fruit can possess good antioxidant and anti-inflammatory activity rendering it a functional food. Since jujube fruit has diverse biological activity, further biological studies including clinical-based studies are recommended to explore the health promoting effect of jujube.

Iterated Virtual Screening-Assisted Antiviral and Enzyme Inhibition Assays Reveal the Discovery of Novel Promising Anti-SARS-CoV-2 with Dual Activity

Unfortunately, COVID-19 is still a threat to humankind and has a dramatic impact on human health, social life, the world economy, and food security. With the limited number of suggested therapies under clinical trials, the discovery of novel therapeutic agents is essential. Here, a previously identified anti-SARS-CoV-2 compound named Compound 13 (1,2,5-Oxadiazole-3-carboximidic acid, 4,4′-(methylenediimino) bis,bis[[(2-hydroxyphenyl)methylene]hydrazide) was subjected to an iterated virtual screening against SARS-CoV-2 Mpro using a combination of Ligand Designer and PathFinder. PathFinder, a computational reaction enumeration tool, was used for the rapid generation of enumerated structures via default reaction library. Ligand designer was employed for the computerized lead optimization and selection of the best structural modification that resulted in a favorable ligand–protein complex. The obtained compounds that showed the best binding to Mpro were re-screened against TMPRSS2, leading to the identification of 20 shared compounds. The compounds were further visually inspected, which resulted in the identification of five shared compounds M1–5 with dual binding affinity. In vitro evaluation and enzyme inhibition assay indicated that M3, an analogue of Compound 13 afforded by replacing the phenolic moiety with pyridinyl, possesses an improved antiviral activity and safety. M3 displayed in vitro antiviral activity with IC50 0.016 µM and Mpro inhibition activity with IC50 0.013 µM, 7-fold more potent than the parent Compound 13 and potent than the antivirals drugs that are currently under clinical trials. Moreover, M3 showed potent activity against human TMPRSS2 and furin enzymes with IC50 0.05, and 0.08 µM, respectively. Molecular docking, WaterMap analysis, molecular dynamics simulation, and R-group analysis confirmed the superiority of the binding fit to M3 with the target enzymes. WaterMap analysis calculated the thermodynamic properties of the hydration site in the binding pocket that significantly affects the biological activity. Loading M3 on zinc oxide nanoparticles (ZnO NPs) increased the antiviral activity of the compound 1.5-fold, while maintaining a higher safety profile. In conclusion, lead optimized discovery following an iterated virtual screening in association with molecular docking and biological evaluation revealed a novel compound named M3 with promising dual activity against SARS-CoV-2. The compound deserves further investigation for potential clinical-based studies.

A Birds-Eye (Re)View of Acid-Suppression Drugs, COVID-19, and the Highly Variable Literature.

This Perspective examines a recent surge of information regarding the potential benefits of acid-suppression drugs in the context of COVID-19, with a particular eye on the great variability (and, thus, confusion) that has arisen across the reported findings, at least as regards the popular antacid famotidine. The degree of inconsistency and discordance reflects contradictory conclusions from independent, clinical-based studies that took roughly similar approaches, in terms of both experimental design (retrospective, observational, cohort-based, etc.) and statistical analysis workflows (propensity-score matching and stratification into sub-cohorts, etc.). The contradictions and potential confusion have ramifications for clinicians faced with choosing therapeutically optimal courses of intervention: e.g., do any potential benefits of famotidine suggest its use in a particular COVID-19 case? (If so, what administration route, dosage regimen, duration, etc. are likely optimal?) As succinctly put this March in Freedberg et al. (2021), “…several retrospective studies show relationships between famotidine and outcomes in COVID-19 and several do not.” Beyond the pressing issue of possible therapeutic indications, the conflicting data and conclusions related to famotidine must be resolved before its inclusion/integration in ontological and knowledge graph (KG)–based frameworks, which in turn are useful for drug discovery and repurposing. As a broader methodological issue, note that reconciling inconsistencies would bolster the validity of meta-analyses which draw upon the relevant data-sources. And, perhaps most broadly, developing a system for treating inconsistencies would stand to improve the qualities of both 1) real world evidence-based studies (retrospective), on the one hand, and 2) placebo-controlled, randomized multi-center clinical trials (prospective), on the other hand. In other words, a systematic approach to reconciling the two types of studies would inherently improve the quality and utility of each type of study individually.

The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease

We aimed to elucidate the frequency of polymorphic genotypes and alleles of patatin-like phospholipase domain containing 3 rs738409 polymorphism and its possible associations with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis in a cohort from Turkey.We enrolled 200 patients diagnosed with NAFLD and genotyped for rs738409 I148M polymorphism by real-time polymerase chain reaction, particularly by melting curve analysis. SPSS analysis software was used for statistical significance. Continuous variable values were expressed as mean ± standard deviation. Significant statistical level was chosen as p = 0.05.Our results demonstrate in a cohort from Turkey that rs738409 C > G polymorphism (I148M) of patatin-like phospholipase domain containing 3 gene is significantly able to affect individuals to have NAFLD in unadjusted regression model.Consistent with the previous studies in other populations, our study group showed a significantly higher risk of having NAFLD in unadjusted regression model but not in the adjusted model indicating that non-genetic factors such as age and sex may be responsible for the association. However, independent studies need to validate our findings with a larger group of NAFLD patients, as well as in different ethnic cohorts.

24-HR AMBULATORY BLOOD PRESSURE MONITORING &amp; ACTIGRAPHY-MEASURED SLEEP DISTURBANCES

Objective: Non-dippers tend to have a high risk for cardiovascular disease. Actigraphy has been validated for objective measures of sleep in clinical-based and population-based studies. PURPOSE: The purpose of this study was to assess Actigraphy measured sleep disturbances among dippers and non-dippers. Design and method: Thirteen (6F/7 M) relatively healthy and clinically free of any sleep-related disorder were recruited. 24-hr Ambulatory blood pressure (BP) monitor applied to the non-dominant arm was used to profile dipping and nondipping status (awake value - sleep value)/awake value &lt; 0.1. 24-hr wrist (dominant arm) Actigraphy data were collected in 1 min epochs, and the ‘Cole-Kripke’ sleep algorithm for adults was used to assess sleep. Sleep disturbance metrics including sleep efficiency, total min in bed, total sleep time, number of awakenings, long wake after sleep onset (WASO: number of min awake between sleep onset and time of final waking) were assessed. Results: Awake SBP (Mean ± SD) for non-dippers (N = 7) 120.2 ± 8.1 vs. dippers 129.1 ± 8.1mmHg; sleep SBP for non-dippers 117.2 ± 8.4 vs. dippers 114.3 ± 5.5mmHg. Non-dippers vs. dippers sleep efficiency (85 vs. 89%); total min in bed (408 vs. 450 min); total sleep time (352 vs. 398 min); number of awakenings (21.1 ± 10.2 vs. 21.1 ± 3.1) were not statistically different. WASO for non-dippers 55.5 ± 32.5 vs. dippers 49.5 ± 18.2 min (p &lt; 0.05). Conclusions: In our preliminary study with a very small N, WASO was 10% higher in non-dippers compared to dippers despite having similar number of awakenings. This indicates that participants with a non-dipper blood pressure profile have disturbed sleep with being awake for a greater amount of time between sleep onset and time of final waking when compared to dippers. Thus, sleep assessment among non-dippers might be reasonable.

Why Concurrent CDDP and Radiotherapy Has Synergistic Antitumor Effects: A Review of In Vitro Experimental and Clinical-Based Studies.

Chemo-radiotherapy, which combines chemotherapy with radiotherapy, has been clinically practiced since the 1970s, and various anticancer drugs have been shown to have a synergistic effect when used in combination with radiotherapy. In particular, cisplatin (CDDP), which is often the cornerstone of multi-drug combination cancer therapies, is highly versatile and frequently used in combination with radiotherapy for the treatment of many cancers. Therefore, the mechanisms underlying the synergistic effect of CDDP and radiotherapy have been widely investigated, although no definitive conclusions have been reached. We present a review of the combined use of CDDP and radiotherapy, including the latest findings, and propose a mechanism that could explain their synergistic effects. Our hypothesis involves the concepts of overlap and complementation. “Overlap” refers to the overlapping reactions of CDDP and radiation-induced excessive oxidative loading, which lead to accumulating damage to cell components, mostly within the cytoplasm. “Complementation” refers to the complementary functions of CDDP and radiation that lead to DNA damage, primarily in the nucleus. In fact, the two concepts are inseparable, but conceptualizing them separately will help us understand the mechanism underlying the synergism between radiation therapy and other anticancer drugs, and help us to design future radiosensitizers.

The importance of clinically relevant background therapy in cardioprotective studies

Treatment of acute myocardial infarct patients (AMI) includes rapid restoration of coronary blood flow and pharmacological therapy aimed to prevent pain and maintain vessel patency. Many interventions have been investigated to offer additional protection. One such intervention is remote ischaemic conditioning (RIC) involving short-episodes of ischaemia of the arm with a blood pressure cuff, followed by reperfusion to protect the heart organs from subsequent severe ischaemia. However, the recent CONDI2-ERIC-PPCI multicentre study of RIC in STEMI showed no benefit in clinical outcome in low risk patients. It could also be argued that these patients were already in a partially protected state, highlighting the disconnect between animal- and clinical-based outcome studies. To improve potential translatability, we developed an animal model using pharmacological agents similar to those given to patients presenting with an AMI, prior to PPCI. Rats underwent MI on a combined background of an opioid agonist, heparin and a platelet-inhibitor thereby allowing us to assess whether additional cardioprotective strategies had any effect over and above this “cocktail”. We demonstrated that the “background drugs” were protective in their own right, reducing MI from 57.5 ± 3.7% to 37.3 ± 2.9% (n = 11, p < 0.001). On this background of drugs, RIC did not add any further protection (38.0 ± 3.4%). However, using a caspase inhibitor, which acts via a different mechanistic pathway to RIC, we were able to demonstrate additional protection (20.6 ± 3.3%). This concept provides initial evidence to develop models which can be used to evaluate future animal-to-clinical translation in cardioprotective studies.

Going beyond the mean: Intraindividual variability of cognitive performance in prodromal and early neurodegenerative disorders

Objective: Intraindividual variability (IIV), generally defined as short-term variations in behavior, has been proposed as a sign of subtle early impairment in neurodegenerative disorders, presumably associated with the disintegration of neuronal network connectivity. We aim to provide a review of IIV as a sensitive cognitive marker in prodromal neurodegenerative disorders.Method: A narrative review focusing not only on theoretical and methodological definitions, including an overview on the neural correlates of IIV, but mainly on results from population-based and clinical-based studies on the role of IIV as a reliable predictor of mild cognitive impairment (MCI) and conversion to dementia in neurodegenerative disorders, mostly Alzheimer’s and Parkinson’s disease.Results: Most studies focus on MCI and Alzheimer’s disease and demonstrate that IIV is a reliable cognitive marker. IIV is partly more sensitive than mean performance in the prediction of cognitive impairment or progressive deterioration and is independent of socio-demographic variables and disease mediators (e.g., genetic susceptibility). Neuroimaging data, mostly from healthy subjects, suggest a relationship between IIV and dysfunction of the default mode network, presumably mediated by white matter disintegration in frontal and parietal areas.Conclusions: IIV measures may provide valuable information about diagnosis and progression in prodromal stages of neurodegenerative disorders. Thus, further conceptual and methodological clarifications are needed to justify the inclusion of IIV as a sensible cognitive marker in routine clinical neuropsychological assessment.

Association of Diabetes With Central Corneal Thickness Among a Multiethnic Asian Population

Thicker or thinner central corneas may lead to either overestimation or underestimation of intraocular pressure, which is the most important causal and treatable risk factor for glaucoma. However, the findings on the associations between diabetes, random glucose, and glycated hemoglobin A1c (HbA1c) with central corneal thickness (CCT) are conflicting. To evaluate the associations between diabetes, random glucose, and HbA1c with CCT in a multiethnic Asian population. Cross-sectional analysis of the Singapore Epidemiology of Eye Diseases (SEED) Study conducted from 2004 to 2011. A total of 10 033 Chinese, Malay, and Indian individuals 40 years or older residing in Singapore were recruited. Participants with incomplete information on diabetes status (448 participants), prior refractive or cataract surgery (1940 eyes), and corneal edema or dystrophy (29 eyes) were excluded. A meta-analysis was conducted to estimate the overall association of diabetes with CCT. Standardized clinical examinations and interviewer-administered questionnaire to collect information about demographic, systemic, and ocular factors. Measurement of CCT using ultrasound pachymetry. A total of 8846 adults (mean [SD] age, 57.9 [9.9] years; 4447 women [50.3%]) (17 201 eyes) were included in the final analyses. The CCT profile was similar among participants with and without diabetes (mean [SD] CCT, 545.3 [33.7] μm vs 544.8 [33.9] μm; P = .39). Following adjustments of age, sex, ethnicity, corneal curvature, axial length, and body mass index, CCT was a mean (SD) of 4.9 (0.8) μm (95% CI, 3.3-6.5 μm) thicker in patients with diabetes than those without diabetes. Multivariable analyses also showed that thicker CCT was associated with higher random glucose (per 10 mg/dL [to convert to mmol/L, multiply by 0.0555], β = 0.3; 95% CI, 0.2-0.4) and higher HbA1c (per percentage, β = 1.5; 95% CI, 1.0-2.1) (all P < .001). These associations were significant in the subgroup with diabetes but not in the subgroup without diabetes. A meta-analysis including 12 previous population- and clinical-based studies showed that CCT was 12.8 μm (95% CI, 8.2-17.5 μm) thicker in eyes of patients with diabetes. These findings suggest that diabetes and hyperglycemia were associated with thicker CCT. This study provides useful information on the interpretation of intraocular pressure in patients with diabetes.

Philosophical Issues and Psychological Variables that Influence the Determination of Opioid Effectiveness: A Narrative Review

Background: The prescribing of opioids in the chronic pain setting is often based on the pharmacodynamics, pharmacokinetics, and pharmacogenetics of the drug obtained during development and clinical trials. However, the effectiveness of opioids varies widely and often appears to bear no relationship to the aforementioned variables. The impact of philosophical issues and psychological factors on determining how clinically effective opioid therapy is has often been over looked. Objectives: This manuscript provides a selective review and narrative summary of the philosophical issues and psychological factors which can influence opioid effectiveness. Study Design: A selective review and narrative analysis of the literature. Methods: Experimental and clinical-based studies examining the impact of psychological factors on the effectiveness of opioids were extracted from the literature. Studies in which psychological factors were used as an independent variable were given preference. Results: The philosophical issues reviewed include: (a) one’s understanding of the nature of chronic pain, (b) the meaning of the score on the pain numerical rating scale (NRS), and (c) the selection of outcome measures. The psychological factors found to influence the effectiveness of opioids include: (a) role conditioning and learning, especially as they relate to conditioned analgesia, non-associative tolerance, and the nocebo effect, (b) dosing pattern, (c) patient specific factors, e.g., mood, overall psychological and neurocognitive status, (d) social variables, e.g., personal environment and the media, and (e) the dysfunctional endogenous opioid system and its relationship to various psychological disorders. Limitations: This is a selective review of the literature. Some of the hypotheses presented have not been experimentally validated. The review includes animal, human, experimental, and clinical studies. Conclusions: In general, the effectiveness of opioids may be influenced as much by the overall context in which they are used, including the physician-patient relationship as well as their pharmacological properties. Data obtained from short-term and well-controlled trials may not generalize to the clinical setting, which is often more complex and dynamic. Appreciating the impact of psychological factors may assist the clinician in proper patient selection, monitoring, and improved outcomes. Key words: Psychological factors, philosophical issues, chronic pain, opioid therapy, effectiveness, conditioning, placebo, cognitive dysfunction

GW28-e0837 Fibroblast growth factor 21 mediates the anti-atherosclerotic action of fenofibrate by activation of PON1 and suppression of SREBP-2 in mice

Numbers animal- and clinical-based studies demonstrate that fibrates, an agonist of peroxisome proliferator-activated receptors, are widely used in clinics for its beneficial effect of anti-hyperlipidemia and cardiovascular disease. However, its exact mechanism required further investigated. This

Design, Implementation, and Assessment Approaches Within a Pharmacogenomics Course

Objective. To design and implement a pharmacogenomics course that focuses on analysis and integration of pharmacogenomic data into clinical practice and to explore how participation in the course influences student self-confidence. Design. The Basic and Clinical Pharmacogenomics course content was divided into three modules: genetic-based didactic sessions, genomic techniques and self-genotype/phenotype laboratory exercise, and clinical-based case studies. Student learning assessment included knowledge- and application-based tests and performance on a group project. Assessment. Effectiveness of the course was evaluated using results of student performance on coded test questions, student perceptions on pre- and post-course self-assessments, performance on a group project, and course evaluation results. Student pharmacists successfully demonstrated competency in pharmacogenomics knowledge-based learning, demonstrated their abilities to apply learned skills in clinical-based scenarios, and reported improved confidence in analyzing patient-based genomic testing results. Conclusions. This course appears to have contributed to student learning and positively influenced student self-confidence in pharmacogenomics.