Background
Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high‐fat meals. Intestinal ...alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes.
Methods
Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short‐chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high‐fat diet for 11 weeks.
Results
Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly.
Conclusion
Deprivation of protective intestinal factors may increase the risk of inflammation in the gut – a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation‐driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion.
The health-related quality of life (HRQOL) of patients with myocardial infarction (MI) is suboptimal because of the disease's life-threatening nature, the requirement for long-term lifestyle ...modifications, and the treatment regimens following MI. This study aimed to evaluate HRQOL and its associated factors in MI patients.
This study was conducted on patients with MI who attended the outpatient cardiology clinic at a major teaching hospital in Jordan. The EQ-5D-3L questionnaire was used to assess HRQOL of the study participants. Quantile regression analysis was conducted to identify the variables associated with HRQOL.
The study included 333 patients with a history of MI, with a median age of 58 (57-60). The median of the total EQ-5D score was 0.65 (0.216-0.805). Regression results revealed that male patients (Coefficient= 0.110, 95%Cl (0.022-0.197), P=0.014) and not being diagnosed with diabetes (Coefficient= 0.154, 95%Cl (0.042-0.266), P=0.007) were associated with increased HRQOL. On the other hand, low income (Coefficient= -0.115, 95%Cl (-0.203 - -0.026), P=0.011), not receiving DPP-4 (Dipeptidyl Peptidase -4) inhibitors (Coefficient= -0.321 95%Cl (-0.462 - -0.180), P<0.001), and having low (Coefficient= -0.271, 95%Cl (-0.395 - -0.147), P<0.001) or moderate (Coefficient= -0.123, 95%Cl (-0.202 - -0.044), P=0.002) medication adherence was associated with decreased HRQOL.
The current study demonstrated diminished HRQOL among patients with MI, highlighting the necessity of tailoring interventions to tackle medication adherence barriers in this population. Personalized interventions such as educational programs, counseling, and reminders that consider each patient's needs and circumstances can greatly enhance medication adherence and, thus, the HRQOL of MI patients. Individuals with lower income levels, female patients, and those with diabetes should be the specific targets of these interventions.
To investigate knowledge, attitude, and practice of asthma management counseling and the perceived barriers by community pharmacists.
This cross-sectional study was conducted on 416 community ...pharmacists using an online-based questionnaire. The questionnaire included five parts that assessed socio-demographics and medical references used to seek drug-related information, pharmacists' knowledge (7 items), attitudes (5 items), practice (22 items) and the barriers for the provision of asthma management counseling (10 items). Binary logistic regression was conducted to find the variables that were significantly and independently associated with knowledge, attitude and asthma management counseling practice.
Increased years of experience was associated with decreased knowledge (OR = 0.918, 95% Cl (0.869:0.970), P = 0.002) and less positive attitude toward asthma management (OR = 0.876, 95% Cl. (0.821:0.935), P < 0.001), while working in independent community pharmacy (OR = 2.097, 95% Cl. (1.273:3.454), P = 0.004) and increased awareness of asthma management guidelines (OR = 1.60, 95% CI. (1.044:2.453), P = 0.031) increased the odds of being in the high knowledge group. In contrast, increasing the daily number of pharmacy visitors OR = 1.009, 95% Cl. (1.001:1.016), P = 0.024) and having a pharmacy degree (OR = 2.330, 95% Cl. (1.256:4.326), P = 0.007) increased the odds of having a positive attitude. Male pharmacists (OR = 0.553, 95% Cl. (0.350:0.873), P = 0.011) and having bachelor in pharmacy (OR = 0.354, 95% Cl. (0.179:0.700), P = 0.003) decreased the odds of being in the high practice group. On the other hand, increased awareness of asthma management guidelines tripled the odds of being in the high practice group (OR = 3.067, 95% Cl. (1.964:4.787), P < 0.001).
The current study findings offer valuable insights into the gaps in knowledge, attitude, and practice of asthma management counseling among community pharmacists, as well as the barriers and factors that impede the provision of these services. These insights serve as a guide for developing future strategies aimed at enhancing the role of pharmacists in asthma care.
Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of ...intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.
This study aimed to assess the confidence, attitude, and scientific research practices of undergraduate students of different health profession specialties.
In this cross-sectional study, an ...online-based questionnaire was distributed as a Google Form via groups and pages of medical universities available on social media sites such as Facebook, WhatsApp, and Twitter to the second- to sixth-year students of different health profession specialties in different universities across the United Arab Emirates (UAE) in the period from October through December 2023 using the convenience sampling technique. The questionnaire included four parts that assessed socio-demographics and custom-designed research-related questions (6 items), perceived confidence (8 items), attitudes (14 items), and the practice in the context of scientific research and its implementation (9 items). Multivariate logistic regression analyses were conducted to explore the variables associated with the study outcomes, including confidence, attitudes, and practice levels.
The study included 522 undergraduate students. The participants reported low confidence, a negative attitude, and low scientific research practice. Regression results revealed that individuals without prior research experiences were less likely to have high confidence and practice compared to those with previous research experience (OR = 0.634, 95% CI: 0.426-0.945, p = 0.025; and OR = 0.139, 95%Cl: 0.090-0.216, P<0.001, respectively). Additionally, participants who reported difficulty in differentiating between various literature resources were less likely to have high confidence and practice compared to those who reported the ability to differentiate (OR = 0.627, 95% CI: 0.42-0.935, p = 0.022, and OR = 0.370, 95%Cl: 0.237-0.579, p<0.001, respectively). Furthermore, individuals who had not taught research methods in their undergraduate studies were less likely to have high practice (OR = 0.505, 95%Cl: 0.309-0.823, p = 0.06).
Undergraduates of different medical specialties in the UAE demonstrated acceptable levels of confidence and attitude toward scientific research, with several areas for practice improvement. Education and training courses focusing on various aspects of scientific research should be incorporated into the medical curricula in order to enhance students' confidence and practice of scientific research.
Despite the cardiovascular disease (CVD) risk associated with hypertension, diabetes, dyslipidemia, and smoking, these risk factors remain poorly identified and controlled.
The study sought to ...evaluate the effectiveness of a community pharmacy-based case finding and intervention on cardiovascular risk.
The RxEACH (Alberta Vascular Risk Reduction Community Pharmacy Project) study was a randomized trial conducted in 56 community pharmacies. Participants were recruited by their pharmacist, who enrolled adults at high risk for CVD. Patients were randomized to usual care (usual pharmacist care with no specific intervention) or intervention, comprising a Medication Therapy Management review from their pharmacist and CVD risk assessment and education. Pharmacists prescribed medications and ordered laboratory tests as per their scope of practice to achieve treatment targets. Subjects received monthly follow-up visits for 3 months. The primary outcome was difference in change in estimated CVD risk between groups at 3 months. CVD risk was estimated using the greater of the Framingham, International, or United Kingdom Prospective Diabetes Study risk scores.
We enrolled 723 patients (mean 62 years of age; 58% male, and 27% smokers). After adjusting for baseline values and center effect, there was a 21% difference in change in risk for CVD events (p < 0.001) between the intervention and usual care groups. The intervention group had greater improvements in low-density lipoprotein cholesterol (-0.2 mmol/l; p < 0.001), systolic blood pressure (-9.37 mm Hg; p < 0.001), glycosylated hemoglobin (-0.92%; p < 0.001), and smoking cessation (20.2%; p = 0.002).
The RxEACH study was the first large randomized trial of CVD risk reduction by community pharmacists, demonstrating a significant reduction in risk for CVD events. Engagement of community pharmacists with an expanded scope of practice could have significant public health implications. (The Alberta Vascular Risk Reduction Community Pharmacy Project: RxEACH RxEACH; NCT01979471).
Optical coherence tomography (OCT) is a noninvasive, depth-resolved imaging modality that has become a prominent ophthalmic diagnostic technique. We present a semi-automated segmentation algorithm to ...detect intra-retinal layers in OCT images acquired from rodent models of retinal degeneration. We adapt Chan-Vese's energy-minimizing active contours without edges for the OCT images, which suffer from low contrast and are highly corrupted by noise. A multiphase framework with a circular shape prior is adopted in order to model the boundaries of retinal layers and estimate the shape parameters using least squares. We use a contextual scheme to balance the weight of different terms in the energy functional. The results from various synthetic experiments and segmentation results on OCT images of rats are presented, demonstrating the strength of our method to detect the desired retinal layers with sufficient accuracy even in the presence of intensity inhomogeneity resulting from blood vessels. Our algorithm achieved an average Dice similarity coefficient of 0.84 over all segmented retinal layers, and of 0.94 for the combined nerve fiber layer, ganglion cell layer, and inner plexiform layer which are the critical layers for glaucomatous degeneration.
Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia ...has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet–induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.
Background Intestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and well-being. Oral supplementation with IAP in mice improves gut barrier function and prevents ...luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function. Study Design The effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice. Regulation of TJPs by IAP was assayed in the human colon cancer Caco-2 and T84 cells by overexpressing the human IAP gene. Tight junction protein levels and localization were measured by using RT q-PCR and antibodies targeting the specific TJPs. Finally, the effect of IAP on inflammation-induced intestinal permeability was measured by in vitro trans-well epithelial electrical resistance (TEER). Results Intestinal alkaline phosphatase gene deletion in MEFs resulted in significantly lower levels of ZO-1, ZO-2, and Occludin compared with levels in wild-type control cells; IAP overexpression in Caco-2 and T84 cells resulted in approximate 2-fold increases in the mRNA levels of ZO-1 and ZO-2. The IAP treatment ameliorated lipopolysaccharide-induced increased permeability in the Caco-2 trans-well system. Furthermore, IAP treatment preserved the localization of the ZO-1 and Occludin proteins during inflammation and was also associated with improved epithelial barrier function. Conclusions Intestinal alkaline phosphatase is a major regulator of gut mucosal permeability and appears to work at least partly through improving TJP levels and localization. These data provide a strong foundation to develop IAP as a novel therapy to maintain gut barrier function.