Uncontrolled Levels Research Articles

Correlation Between Magnesium and HbA1C in Type 2 Diabetes Mellitus

Background: Magnesium (Mg) is most abundant electrolyte with unlimited physiologic importance in the body, playing a vital role in many fundamental processes. Cellular magnesium is an essential cofactor for various enzymes involved in glucose transport, insulin release and glucose oxidation. Mg has potential role in improving insulin sensitivity and preventing diabetes and its complications. Hypomagnesemia promotes to the initiation and progression of DM and its macrovascular and microvascular complications. Objectives: The aim of this study was to evaluate the correlation of magnesium with HbA1C in T2DM. Material and Methods: This cross sectional study conducted at Tribhuvan University Teaching Hospital, included 85 diagnosed with type 2 diabetes Mellitus visiting Medicine OPD and 85 apparently healthy controls. Clinical and anthropometric characteristics were documented using clinical proforma. The fasting blood samples were collected for estimating serum glucose, HbA1C and magnesium. Results: The mean values of BMI, FBG, HbA1C were found to be significantly elevated in T2DM, but that of Mg were higher in healthy controls (p<0.05). The prevalence of hypomagnesemia in T2DM was found to be 32.94%. The Serum magnesium levels were moderate negatively correlated (r = -0.544, P<0.001) with HbA1C. Conclusion: Patient with Type 2 Diabetes Mellitus showed significantly low magnesium levels compared to heathy controls as well as uncontrolled HbA1C levels also showed significantly low magnesium level than controlled HbA1C level. There was significant inverse correlation between serum Mg level and HbA1C level in patients with T2DM. So if serum magnesium values are made to rise, HbA1C values will fall.

The abundance change of age-regulated secreted proteins affects lifespan of C. elegans

Proteome integrity is vital for survival and failure to maintain it results in uncontrolled protein abundances, misfolding and aggregation which cause proteotoxicity. In multicellular organisms, proteotoxic stress is communicated among tissues to maintain proteome integrity for organismal stress resistance and survival. However, the nature of these signalling molecules and their regulation in extracellular space is largely unknown. Secreted proteins are induced in response to various stresses and aging, indicating their roles in inter-tissue communication. To study the fates of age-regulated proteins with potential localization to extracellular, we analysed publicly available age-related proteome data of C. elegans. We found that abundance of majority of the proteins with signal peptides (SP) increases with age, which might result in their supersaturation and subsequent aggregation. Intriguingly, these changes are differentially regulated in the lifespan mutants. A subset of these SP proteins is also found in the cargo of extracellular vesicles. Many of these proteins are novel and functionally uncharacterized. Reducing levels of a few extracellular proteins results in increasing lifespan. This suggests that uncontrolled levels of extracellular proteins might disturb proteostasis and limit the lifespan. Overall, our findings suggest that the age-induced secreted proteins might be the potential candidates to be considered as biomarkers or for mitigating age-related pathological conditions.

Hubungan Antara Kadar HbA1c dengan Kadar Trigliserida terhadap Pasien Prolanis Diabetes Melitus Tipe 2 di Laboratorium Klinik Kimia Farma Depok

Diabetes Mellitus (DM) is a group of metabolic disorders characterized by elevated blood glucose levels resulting from abnormalities in insulin secretion, insulin action, or both. Patients with Type 2 DM are at a higher risk of developing cardiovascular diseases, often indicated by dyslipidemia, which is characterized by elevated triglyceride levels, increased Low-Density Lipoprotein (LDL) levels, and decreased High-Density Lipoprotein (HDL) levels. This study employs an analytical observational design. The data obtained shows that controlled and uncontrolled HbA1c levels with normal triglyceride levels were found in 24.7% of the patients, while 75.3% had high triglyceride levels. The data were further analyzed using the Statistical Package for the Social Sciences 25 (SPSS 25) with a non-parametric test, specifically the Chi-Square continuity correction test, with a significance level of p 0.05. The Chi-Square test results indicated that H0 was rejected and Ha was accepted, with a p-value of 0.036 for the relationship between HbA1c and triglycerides. These results suggest a correlation between HbA1c levels and triglyceride levels in Prolanis Type 2 DM patients at Kimia Farma Clinical Laboratory in Depok. These findings can serve as an evaluation material for Prolanis DM Type 2 patients to control their glycemic levels by routinely monitoring their HbA1c and triglyceride levels.

Patients’ perceptions on reluctance to undergo cataract surgery in Sedibeng district hospital, Gauteng province

Background: Over 50 million people are blind, and 135 million people suffer from severe visual impairments, with cataracts contributing to 51% of global blindness cases. Despite efforts to promote cataract surgery (CS), many patients remain hesitant, underscoring the importance of understanding their perspectives.Aim: This study aimed to explore and describe patients’ perceptions regarding reluctance to undergo CS to improve awareness and increase surgery uptake.Setting: The research was conducted in the Sedibeng District, Gauteng province, South Africa.Methods: A qualitative descriptive phenomenological design was employed to capture the lived experiences of patients through face-to-face, individual semi-structured interviews with 15 patients aged 38 – 72 years prior to their CS. Purposive sampling was used to select participants, and Colaizzi’s seven-step analysis was used for data analysis.Results: The findings highlight several barriers perceived by participants, including long waiting times; fear; lack of knowledge; limited financial, material and human resources; power outages; uncontrolled blood sugar levels; and coronavirus disease 2019 (COVID-19) pandemic restrictions. Nevertheless, some view it positively as a means to avert blindness and enhance vision.Conclusion: To address the challenges, the study recommends boosting the number of eye health care professionals, prioritising budget allocation, addressing electricity interruptions and conducting community outreach educational programmes to improve access to CS in the district.Contribution: The insights gained from this study can help health care providers and policymakers optimise care and support for CS patients through policy formulation and education. Addressing these knowledge gaps will likely increase surgery uptake and improve patients’ quality of life.

Hypertension and diabetes control: faith-based centres offer a promise for expanding screening services and linkage to care in Ghana

BackgroundHypertension and type 2 diabetes mellitus (T2DM) are important contributors to noncommunicable disease related morbidity and mortality. Health systems could benefit from exploring the use of Faith-Based Centres (FBC) to screen and link suspected cases for further care in order to help achieve Sustainable Development Goal (SDG) 3. The study investigated the role of faith-based screening for T2DM and hypertension and the linkage of cases to the healthcare system and examined the care cascade in the Kassena Nankana Districts of Northern Ghana.MethodsWe screened individuals from 6 FBCs for elevated blood pressure and hyperglycaemia. Suspected hypertension and T2DM cases were referred to health facilities for confirmation and subsequently followed them up for 3 months. We assessed the prevalence of behavioural and metabolic risk factors, including hypertension and T2DM, and the retention of referred cases in the healthcare system over follow up period. We further assessed levels of awareness, treatment and adequate control of hypertension and T2DM.ResultsA total of 631 participants were screened, (mean age 49 ± 16years, 73% female) from 6 Faith based Centres. More males than females reported smoking tobacco (14.5% vs. 0.7%) and been physically active (64.5% vs. 52.7%) while more females were obese (29.6 kg/m2 vs. 14.5 kg/m2) and had a higher mean waist circumference (89.0 cm IQR 75-116 cm vs. 84.2 cm IQR 72–107 cm), hip circumference (101.5 ± 10.6 cm vs. 96.4 ± 8.6 cm) and waist-to-hip ratio (0.86 ± 0.1 cm vs. 0.87 ± 0.1 cm) than males. The prevalence of confirmed hypertension and T2DM was 27.9% and 3.5% respectively with no observed sex differences. We observed deficits in the hypertension and T2DM care cascade with reported low awareness, treatment and uncontrolled levels. A 3-month follow up showed a retention in care of 100% in month one and 94.9% in the third month. There was an increase in treatment (39.4% in month-1 and 82.8% in month-3) and control (26.3% in month-1 and 76.3% in month-3) of hypertension and T2DM combined.ConclusionFaith-based centres have the potential to enhance the screening, linkage to the healthcare system, and management of hypertension and T2DM. This improvement over the routine system could lead to earlier diagnoses, a reduction in complications, and decreased premature mortality from cardiovascular diseases. Consequently, these efforts would contribute significantly to achieving SDG 3.

Exploring the association of social connections and food security among adults with uncontrolled type 2 diabetes: a population-based study

BackgroundPrimary health care professionals are held accountable for various quality measures in the treatment of patients with chronic diseases such as diabetes. Uncontrolled type 2 diabetes (T2D) remains a considerable health problem; thus, further studying patients with this condition is important for delivering effective interventions. Social determinants of health (SDoH) have been shown to affect various aspects of diabetes care in different subpopulations. We studied the association of SDoH with uncontrolled T2D in a population of adult primary care patients.MethodsWe retrospectively searched our electronic health record for adult patients (≥18 years) with a diagnosis of T2D and a hemoglobin A1c (HbA1c) level of 8% or higher. Patients were empaneled to 2 primary care clinic sites between January 1, 2021, and January 31, 2022. Patients were grouped by HbA1c level to stratify patients according to the extent of uncontrolled T2D. Patient characteristics were compared among groups. Unadjusted and adjusted multinomial logistic regression analysis was used to estimate the odds of various SDoH factors among patient groups with different levels of uncontrolled T2D.ResultsThe study cohort included 1,596 patients. Most patients were White (79%), and the median age was 58.8 years. The median HbA1c level was 8.9%, and approximately 68% of patients were obese (body mass index [BMI] ≥30). When the study population was grouped by HbA1c level (8% to < 9% [n = 806], ≥9% to < 12% [n = 684], and ≥12% [n = 106]), significant differences among groups were observed in age group (P < .001), marital status (P < .001), race (P < .001), ethnicity (P = .001), and BMI category (P = .01). In groups with higher HbA1c levels, we noticed a higher percentage of patients who were aged 51 to 65 years or single. Among patients with uncontrolled HbA1c levels, more patients were obese than overweight. Patients in the intermediate HbA1c group had increased odds of food insecurity and some decreased social connections, even after adjusting for age, sex, race, ethnicity, and marital status.ConclusionsAmong patients with uncontrolled T2D, higher HbA1c levels were associated with decreased social connections and increased food insecurity. Our findings provide insight into the role of these SDoH in managing T2D and have important implications for primary care practice.

Prevalence of Diabetic Macular Edema Using Optical Coherence Tomography in Type 2 Diabetics With Nephropathy in Comparison With Type 2 Diabetics Without Nephropathy.

The primary vision-threatening complication in patients with diabetic retinopathy (DR) is diabetic macular edema (DME). Diabetic nephropathy (DN) often has DR that threatens their vision and has a risk of developing DME. Hence, the presence of DN could be the only risk factor for developing DME without the presence of other factors. Hence, this study proposes to predict the prevalence of DME using optical coherence tomography (OCT) in type 2 diabetics with nephropathy in comparison with diabetics without nephropathy. This is a cross-sectional study done on patients visiting the Ophthalmology Department at Saveetha Medical College and Hospital, Chennai, for one year. A total of 120 patients were included in the study, with 60 diabetic patients without nephropathy in Group 1 and 60 diabetic patients with nephropathy in Group 2. A detailed history was recorded. Their recent blood reports of fasting blood sugar, postprandial blood sugar, hemoglobin A1c (HbA1c), renal function test, and urine protein/creatinine ratio were all noted. Chronic kidney disease (CKD) staging in nephropathy patients as done by the nephrologist was also documented. The best corrected visual acuity (BCVA) was assessed for distant and near vision. A slit lamp examination and dilated fundus examination were done. Fundus findings were independently graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) classification. OCT was done in all patients to confirm DME. In our study. males and females were 60 each in number. The majority of patients(32.5%) were >70 years old. A small percentage of patients (1.7%) in Group 1 had DM of >10 years, and 41.7% of the patients in Group 2 had DM of >10 years. Meanwhile, 73.3% of the patients in Group 1 had an HbA1c level between 6% and 7.5%, and 83.3% of the patients in Group 2 had an HbA1c level >7.5%. The percentage of patients with DME in Group 1 was 1.7%, and that in Group 2 was 21.7%. The majority of patients who had BCVA of 6/6 were in Group 1. The majority of patients with DME (46.4%) had stage V nephropathy. The coexistence of nephropathy in diabetic patients increases the incidence of DME. With long-standing diabetes and uncontrolled blood sugar levels being risk factors for developing DN and subsequently DME, such patients are to be screened regularly and advised on adequate glycemic control for achieving good visual prognosis and limit retinopathy progression. Moreover, the severity of DN should be kept in mind by nephrologists, and patients are to be promptly referred to the ophthalmology department for complete evaluation.

BIOACCUMULATION OF CU AND CO IN LEAFY AND FRUIT VEGETABLES FROM THE SUBURBS OF MITROVICA, KOSOVO

Contamination of vegetables with heavy metals is one of the basic environmental problems, especially in developing cities, primarily due to the uncontrolled level of pollution caused by industrial growth and the increase in the number of vehicles using petroleum fuels. This paper aims to determine the bioconcentration of heavy metals Cu and Co in leafy and fruit vegetables grown near Kosovska Mitrovica (Republic of Kosovo). Three places near Kosovska Mitrovica (Zvečan, Frashër, and Polski) are grown: parsley, spinach, lettuce, peppers, eggplant, and cucumber. All analyzed crops are from the 2023 harvest. In the same period, an analysis was made of the soil on which the crops were grown. The bioconversion factor (BF)of the selected leafy and fruit vegetables was also determined. The ICP-MS technique was used to determine the concentration of Cu and Co in soil and leafy and fruit vegetables. From the obtained analyzes it was determined that the soil in Frashër contains the highest amount of Cu and Co - 58.4 mg/kg and 11.6 mg/kg respectively. The amount of Cu in the examined dry leafy and fruit vegetables is in the range from 5.38 mg/kg to 22.4 mg/kg, and of Co from 0.27 mg/kg to 2.99 mg/kg. The bioconcentration factor of the studied leafy and fruit vegetables of Cu and Co is in the range of 0.04 to 0.26 and 0.15 to 0.65 respectively. The accumulation of Co in the analyzed vegetables is higher than the accumulation of Cu, due to the higher BF values for Co. The statistical processing of the results (t-test) showed that there is a difference in the concentration of Cu and Co between leafy and fruit vegetables, but there is no statistically significant difference because the obtained p-values are greater than the marginal p-values.

Meta-analysis of bone mineral density in adults with phenylketonuria

BackgroundLifelong management of phenylketonuria (PKU) centers on medical nutrition therapy, including dietary phenylalanine (Phe) restriction in addition to Phe-free or low-Phe medical foods/protein substitutes. Studies have reported low bone mineral density (BMD) in mixed-age PKU populations, possibly related to long-term Phe restriction. Therefore, a meta-analysis investigating BMD specifically in adults with PKU was conducted.MethodsStudies reporting BMD-related outcomes were identified from a systematic literature review evaluating somatic comorbidities experienced by adults with PKU on a Phe-restricted diet (searched February 1, 2022, updated November 1, 2023). Risk of study bias was assessed (Scottish Intercollegiate Guidelines Network checklists). The primary outcome of the meta-analysis was pooled mean BMD Z-scores of different bones. Secondary outcomes were the prevalence of low BMD Z-scores at pre-specified thresholds. Subgroup analyses of mean BMD Z-scores (decade of study publication, controlled versus uncontrolled blood Phe levels, gender) were conducted.ResultsBMD-related data from 4097 individuals across 10 studies rated as at least acceptable quality were included. Mean BMD Z-scores were statistically significantly lower compared with an age-matched control or reference (non-PKU) population, across bones, but still within the expected range for age (> -2.0): lumbar spine (seven studies, n = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies, n = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies, n = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies, n = 157), -0.61 (95% CI: -0.77, -0.45). The small number of observations in the subgroup analyses resulted in a high degree of uncertainty, limiting interpretation. Estimated prevalence of BMD Z-scores ≤ -2.0 was 8% (95% CI: 5%, 13%; four studies, n = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies, n = 144).ConclusionsAdults with PKU had lower BMD Z-scores than the reference (non-PKU) population but < 1 in 10 were below the expected range for age. The low number of studies prevents identification of which population characteristics are most impacting BMD.This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476).

Negative Self-Care Behaviours Among Diabetic Patients Bukittinggi, Indonesia

Diabetes mellitus is a chronic multifactorial endocrine disorder that affects approximately 5-10% of adults worldwide. In Indonesia, approximately 10.8 million people, which accounts for 10% of the population, suffer from diabetes. The current treatment considered suitable for diabetes management involves self-care management. Self-management plays a crucial role in achieving blood sugar control, reducing complications, improving quality of life, and lowering hospitalization rates. Negative self-care behaviors frequently observed among diabetes patients include consuming high-fat foods, sugary snacks, non-adherence to diabetes diet protocols. These unhealthy habits make it more difficult to regulate one's own health, which increases the risk of morbidity and death, uncontrolled blood sugar levels, and a decline in quality of life. The purpose of this study is to identify poor self-care practices among type 2 diabetes patients in the Bukittinggi health facilities' service region. Using a deliberate sample technique, a qualitative descriptive study was carried out in seven operational regions of the community health clinics in Bukittinggi, Indonesia. Participants were interviewed in semi-structured interviews, and a chollezi was used to analyze the data. There were 15 people in all, ages 30 to 69, who participated in this study. The participants had been diagnosed with diabetes for a duration of 2 to 21 years. The study identified four themes: unhealthy dietary behaviors, poor medication adherence, preference of unstandardized based herbal medicine, and surrender to Diabetic. Future research should focus on developing appropriate interventions and health promotion strategies

Volatile Fatty Acids from Household Food Waste: Production and Kinetics

Household food waste (HFW), which is rich in organic matter, is a good candidate for producing added-value bio-based chemicals, such as volatile fatty acids (VFAs), by acidogenic fermentation processes. However, the lack of design tools, such as appropriate kinetic models, hinders the implementation of this technology because the results of these processes are affected by operational factors. In this work, VFA production by the acidogenic fermentation of HFW under uncontrolled pH levels (4–5) was studied at thermophilic (55 °C) and mesophilic (35 °C) temperature conditions. Batch reactors were used to digest HFW, and VFA production and the individual acid distributions were measured at different fermentation times from 0 to 624 h. The results showed higher individual and total VFA production at 35 °C and 120 h of fermentation time as a consequence of the competition between the VFA production and decomposition reactions. Acetic and valeric acids were VFAs mainly produced as a result of a high content of proteins in the initial substrate, and a small amount of propionic and butyric acids were present. A simplified kinetic model was successfully developed to represent the complex process of VFA formation from the acidogenic fermentation of HFW. A simple mechanism for the production–decomposition of VFAs, corresponding to a zero-order reaction for the first 48 h and a single consecutive reaction from that time on, was proposed. For both mesophilic and thermophilic conditions, the suggested kinetic model was able to predict the individual and total concentrations of VFAs along the fermentation time.

Nicotine inhalation and metabolism triggers AOX-mediated superoxide generation with oxidative lung injury

With the increasing use of vaping devices that deliver high levels of nicotine (NIC) to the lungs, sporadic lung injury has been observed. Commercial vaping solutions can contain high NIC concentrations of 150 mM or more. With high NIC levels, its metabolic products may induce toxicity. NIC is primarily metabolized to form NIC iminium (NICI) that is further metabolized by aldehyde oxidase (AOX) to cotinine. We determine that NICI in the presence of AOX is a potent trigger of superoxide generation. NICI stimulated superoxide generation from AOX with Km=2.7 μM and Vmax=794 nmol/min/mg measured by cytochrome-c reduction. EPR spin-trapping confirmed that NICI in the presence of AOX is a potent source of superoxide. AOX is expressed in the lungs and chronic e-cigarette exposure in mice greatly increased AOX expression. NICI or NIC stimulated superoxide production in lungs of control mice with even greater increase after chronic e-cigarette exposure. This superoxide production was quenched by AOX inhibition. Furthermore, e-cigarette-mediated NIC delivery triggered oxidative lung damage that was blocked by AOX inhibition. Thus, NIC metabolism triggers AOX-mediated superoxide generation that can cause lung injury. Therefore, high uncontrolled levels of NIC inhalation, as occur with e-cigarette use, can induce oxidative lung damage.

Hubungan Kadar HbA1c Dengan Kadar Serum Kreatinin Pada Penderita Diabetes Melitus Tipe 2 Di RSU Sinar Kasih Purwokerto

Diabetes Mellitus is a metabolic disorder caused by a decrease in insulin products in the body. The World Health Organization estimates an increase in the number of diabetes mellitus sufferers from 8.4 million in 2000 to around 21.3 million in 2030. Chronic diabetes mellitus sufferers can cause complications, one of which is kidney complications. Kidney damage can occur due to uncontrolled blood sugar levels. Complications of diabetes mellitus can be detected by examining HbA1c. HbA1c is a non-enzymatic binding of glucose molecules to hemoglobin through a post-translational glycation process. Uncontrolled HbA1c levels can cause various complications in the body.The samples used for this research were 106 samples with normal HbA1C examination results, namely 59 patients and high results, namely 47 patients. Creatinine examination with normal results was 81 patients and high results were 25 patients. The P-value from the calculation results is 0.066 higher than 0.005. Based on the results of the chi square calculation, it can be concluded that there is not a relationship between HbA1C examination and creatinine examination in type 2 diabetes mellitus patients at Sinar Kasih Hospital.

The potential role of finerenone in patients with type 1 diabetes and chronic kidney disease.

Chronic kidney disease (CKD) represents a global health concern, associated with an increased risk of cardiovascular morbidity and mortality and decreased quality of life. Many patients with type 1 diabetes (T1D) will develop CKD over their lifetime. Uncontrolled glucose levels, which occur in patients with T1D as well as type 2 diabetes (T2D), are associated with substantial mortality and cardiovascular disease burden. T2D and T1D share common pathological features of CKD, which is thought to be driven by haemodynamic dysfunction, metabolic disturbances, and subsequently an influx of inflammatory and profibrotic mediators, both of which are major interrelated contributors to CKD progression. The mineralocorticoid receptor is also involved, and, under conditions of oxidative stress, salt loading and hyperglycaemia, it switches from homeostatic regulator to pathophysiological mediator by promoting oxidative stress, inflammation and fibrosis. Progressive glomerular and tubular injury leads to macroalbuminuria a progressive reduction in the glomerular filtration rate and eventually end-stage renal disease. Finerenone, a non-steroidal, selective mineralocorticoid receptor antagonist, is approved for treatment of patients with CKD associated with T2D; however, the benefit of finerenone in patients with T1D has yet to be determined. This narrative review will discuss treatment of CKD in T1D and the potential future role of finerenone in this setting.

Effect of hyperbaric oxygen therapy on diabetes- related oral complications

ABSTRACT Altun BD, Sümen SG, Öçbe M, Dumlu A. Effect of hyperbaric oxygen therapy on diabetes-related oral complications. Undersea Hyperb Med. 2024 Second Quarter; 51(2):101-106. Background: Diabetes Mellitus is a chronic disease characterized by uncontrolled blood sugar levels, which lead to end-organ damage. While the diagnosis and treatment of its complications have been extensively studied, the effect of Hyperbaric Oxygen Therapy (HBO2) on diabetes-related oral complications remains unexplored. Aim: This prospective clinical study aims to investigate the effect of HBO2 on diabetes-related oral complications. Methods: Twenty patients diagnosed with diabetic foot ulcers and scheduled for HBO2 were included in this study. We recorded stimulated and unstimulated saliva pH, buffering capacity, flow rate, and subjective symptoms such as dry mouth, halitosis, taste loss, difficulty swallowing, and clinical examination findings before HBO2 and after the 21st session. Results: Upon comparing the findings, we observed a significant decrease in dry mouth and halitosis, periodontal disease severity, and healing of candida-related stomatitis and angular cheilitis. Despite not reaching statistical significance for other saliva parameters, the unstimulated salivary flow rate increased to normal limits (0.3-0.4 ml/min) in 6 out of 8 patients with a flow rate of less than 0.25 ml/min. Conclusion: Our study investigated the effect of HBO2 on diabetes-related oral complications for the first time, highlighting symptomatic relief for dry mouth and halitosis. Although our results are insufficient to report a definitive benefit, they underscore the need for further research on the oral health effects of HBO2.

Tenascin-C is a Promising Marker of High Bone Turnover and Vascular Calcification in Prevalent Hemodialysis Patients

Abstract Background and Aims Tenascin-C (TN-C) is an extracellular matrix glycoprotein associated with high cell turnover and vascular calcification and atherosclerosis. This study determines the frequency of Tenascin-C in uncontrolled parathyroid hormone state and its relation to vascular calcification. Method A cross sectional study included 90 prevalent hemodialysis patients divided into 2 equal groups: uncontrolled iPTH level &amp;gt;300 pg /ml and controlled iPTH (150-300 pg/ml) groups. Serum Tenascin-C was measured by ELISA and vascular calcification was assessed by simple vascular calcification score (adragao score): by Plain X ray on hands, pelvis &amp; vascular access for all patients. Results The prevalence of Tenascin-C and vascular calcification in patient with uncontrolled PTH were 84.4% (38 patients), 46.7% (21 patients) respectively. Tenascin-C was positively correlated with PTH level (r 0.494 p &amp;lt; 0.001) in patients with high bone turnover. Tenascin-C was high in patients with uncontrolled PTH [median (IQR) 637 (4245)u/ml] compared with patients with controlled PTH [median (IQR) 211 (143) u/ml] P value &amp;lt;0.0001. According to Adragao calcification score, in uncontrolled PTH: 31.1% (14 patients) had score 1 and 15.6% (7 patients) score 2. In controlled iPTH all patients had score 0. Patients with vascular calcification had high Tenascin-C median [(IQR) 10697 (53974)] compared with patients without vascular calcification [median (IQR)7697 (18000) u/ml)] P value &amp;lt;0.001. Serum Tenascin-C can predict high bone turnover at cutoff value 7377 ng/ml with AUC 0.794, sensitivity 84.4% and specificity 60 % while predict vascular calcification at cut of value &amp;gt; 8859 ng/ml AUC 0.745, sensitivity 72.7 %, specificity 72.1 %. Patients who have elevated level of tenascin C had 10.3, 3.7 times the risk to have high bone turnover and vascular calcification than negative one respectively. Conclusion Tenascin-C appears to be a sensitive marker for assessment of high bone turnover and vascular calcification in Prevalent Hemodialysis Patients.

Assessment of myocardial microvascular dysfunction in patients with different stages of diabetes mellitus: An adenosine stress perfusion cardiac magnetic resonance study

PurposeTo examine myocardial perfusion and T1 mapping indicesin individuals with type 2 diabetes mellitus (T2DM) at various stages of glycemic control and whether uncontrolled glycemic levels would worsen myocardial microvascular function. MethodCardiac magnetic resonance examinations were performed on 114 T2DM patients without obstructive coronary artery disease and 55 matched controls. Participants were further divided into four subgroups: Q1 (control); Q2 (prediabetes); Q3 (controlled T2DM) and Q4 (uncontrolled T2DM). The correlation between glycosylated hemoglobin (HbA1c) levels and myocardial perfusion parameters was evaluated. ResultsGlobal myocardial perfusion reserve index (MPRI) was significantly reduced in the Q3 and Q4 subgroups compared to the Q1 or Q2 subgroup (all P<0.001). Compared with the Q1 subgroup, global stress T1 reactivity (stress ΔT1) was significantly reduced in the Q3 and Q4 subgroups (P=0.004 and < 0.001, respectively), but elevated in the Q2 subgroup (P=0.018). Global extracellular volume (ECV) was considerably higher in the Q2 subgroup and gradually rose in the Q3 and Q4 subgroups compared to the Q1 subgroup (P=0.011, 0.001, and 0.007, respectively). HbA1c levels correlated negatively with global MPRI and stress ΔT1, but positively with global ECV (β = -1.993, P<0.001; β = -0.180, P<0.001; and β = 0.127, P<0.001, respectively). ConclusionsGlobal stress ΔT1 reduced in T2DM patients but rose in prediabetes patients. Compared to MPRI, the ECV parameter can indicate diabetes-induced coronary microvascular dysfunction earlier and persists throughout the disorder. Myocardial perfusion and T1 mapping at stress can be used to detect early signs of microvascular dysfunction and subclinical risk factors in patients with T2DM.

Neutrophil serine proteases in cystic fibrosis: role in disease pathogenesis and rationale as a therapeutic target.

Chronic airway inflammation is a central feature in the pathogenesis of bronchiectasis (BE), which can be caused by cystic fibrosis (CFBE; hereafter referred to as CF lung disease) and non-CF-related conditions (NCFBE). Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and granule proteins, including neutrophil serine proteases (NSPs). NSPs include neutrophil elastase, proteinase 3 and cathepsin G. An imbalance between NSPs and their antiproteases has been observed in people with CF lung disease and people with NCFBE. While the role of the protease/antiprotease imbalance is well established in both CF lung disease and NCFBE, effective therapies targeting NSPs are lacking. In recent years, the introduction of CF transmembrane conductance regulator (CFTR) modulator therapy has immensely improved outcomes in many people with CF (pwCF). Despite this, evidence suggests that airway inflammation persists, even in pwCF treated with CFTR modulator therapy. In this review, we summarise current data on neutrophilic inflammation in CF lung disease to assess whether neutrophilic inflammation and high, uncontrolled NSP levels play similar roles in CF lung disease and in NCFBE. We discuss similarities between the neutrophilic inflammatory profiles of people with CF lung disease and NCFBE, potentially supporting a similar therapeutic approach. Additionally, we present evidence suggesting that neutrophilic inflammation persists in pwCF treated with CFTR modulator therapy, at levels similar to those in people with NCFBE. Collectively, these findings highlight the ongoing need for new treatment strategies targeting neutrophilic inflammation in CF lung disease.

Simultaneous regulation of AGE/RAGE signaling and MMP-9 expression by an immunomodulating hydrogel accelerates healing in diabetic wounds

PurposeIn chronic hyperglycemia, the advanced glycation end product (AGE) interacts with its receptor (RAGE) and contributes to impaired wound healing by inducing oxidative stress, generating dysfunctional macrophages, and prolonging the inflammatory response. Additionally, uncontrolled levels of proteases, including metallomatrix protease-9 (MMP-9), in the diabetic wound bed degrade the extracellular matrix (ECM) and biological cues that augment healing. A multifunctional antimicrobial hydrogel (Immuno-gel) containing RAGE and MMP-9 inhibitors can regulate the wound microenvironment and promote scar-free healing. ResultsImmuno-gel was characterized and the wound healing efficacy was determined in vitro cell culture and in vivo diabetic Wistar rat wound model using ELISA, Western blot, and Immunofluorescence staining. The Immuno-gel exhibited a highly porous morphology with excellent in vitro cytocompatibility. AGE-stimulated macrophages treated with the Immuno-gel released higher levels of pro-healing cytokines in vitro. In the hydrogel-wound interface of diabetic Wistar rats, Immuno-gel treatment significantly reduced MMP-9 and NF-κB expression and enhanced pro-healing (M2) macrophage population and pro-healing cytokines. ConclusionAltogether, this study suggests that Immuno-gel simultaneously attenuates macrophage dysfunction through the inhibition of AGE/RAGE signaling and reduces MMP-9 overexpression, both of which favor scar-free healing. The combinatorial treatment with RAGE and MMP-9 inhibitors via Immuno-gel simultaneously modulates the diabetic wound microenvironment, making it a promising novel treatment to accelerate diabetic wound healing.

Are Hyperglycemia-Induced Changes in the Retina Associated with Diabetes-Correlated Changes in the Brain? A Review from Zebrafish and Rodent Type 2 Diabetes Models.

Diabetes is prevalent worldwide, with >90% of the cases identified as Type 2 diabetes. High blood sugar (hyperglycemia) is the hallmark symptom of diabetes, with prolonged and uncontrolled levels contributing to subsequent complications. Animal models have been used to study these complications, which include retinopathy, nephropathy, and peripheral neuropathy. More recent studies have focused on cognitive behaviors due to the increased risk of dementia/cognitive deficits that are reported to occur in older Type 2 diabetic patients. In this review, we collate the data reported from specific animal models (i.e., mouse, rat, zebrafish) that have been examined for changes in both retina/vision (retinopathy) and brain/cognition, including db/db mice, Goto-Kakizaki rats, Zucker Diabetic Fatty rats, high-fat diet-fed rodents and zebrafish, and hyperglycemic zebrafish induced by glucose immersion. These models were selected because rodents are widely recognized as established models for studying diabetic complications, while zebrafish represent a newer model in this field. Our goal is to (1) summarize the published findings relevant to these models, (2) identify similarities in cellular mechanisms underlying the disease progression that occur in both tissues, and (3) address the hypothesis that hyperglycemic-induced changes in retina precede or predict later complications in brain.