Deficient Group Research Articles

Vitamin d levels in pediatric epilepsy patients on the anti-epileptic drugs at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

Background: Epilepsy is a common neurological disorder of childhood repeatedly necessitating prolonged use of anticonvulsants. This study was done to evaluate the status of vitamin D in epileptic children. We targeted to describe the prevalence and risk factors for vitamin D deficiency among children with epilepsy. 
 Methods: A hospital-based descriptive cross-sectional study design with prospective data collection was used among children with epilepsy on anti-epileptic drugs attending the Pediatric Neurology Clinic and their primary caretakers. For this study, a sample of 226 children and adolescents were included in the study and a blood sample for the determination of serum vitamin D was taken. The participants were interviewed, and medical records were thoroughly reviewed. Descriptive statistics and binary logistic regression analysis was done to assess determinants of vitamin D deficiency. . 
 Results: In this study, the prevalence of vitamin D deficiency was found to be 42%. Children on polytherapy (AOR = 4.3 (1.2 - 16)), 3 or more AEDs (AOR = 0.1 (0.0 - 0.8)), female sex (AOR = 1.8 (1.7 - 2.6)), age >15 years (AOR = 2.12 (1.0 - 1.5)), 4 months of exclusive breastfeeding (AOR = 5.6 (4.9 - 36)), family diet (AOR = 0.3 (0.1 - 0.8)) and non-ambulation (AOR = 1.7 (1.8 - 3.6)) were factors associated with being in the vitamin D deficiency group.
 Conclusion: According to this study patients who take Anti-Epilepsy drugs are at a higher risk of a poor vitamin D status. Based on this finding, the need for timely and appropriate vitamin D supplementation and periodic follow-up seems to be very evident.

Differential clinical characteristics across traditional Chinese medicine (TCM) Syndromes in patients with sickle cell disease.

Pain is a common, debilitating, and poorly understood complication of sickle cell disease (SCD). The need for clinical pain management of SCD is largely unmet and relies on opioids as the main therapeutic option, which leads to a decreased quality of life (QoL). According to the literature, acupuncture has shown certain therapeutic effects for pain management in SCD. However, these clinical studies lack the guidance of Traditional Chinese Medicine (TCM) Syndrome Differentiation principles for treatment. To characterize differences in clinical presentation amongst TCM diagnosed Syndromes in SCD patients. Fifty-two patients with SCD and 28 age- and sex-matched healthy controls (HCs) were enrolled in an ongoing trial of acupuncture. Each participant completed a series of questionnaires on pain, physical function, fatigue, sleep, anxiety, depression and QoL and underwent cold- and pressure-based quantitative sensory testing at baseline. Data on prescription opioid use over the 12 months prior to study enrollment was used to calculate mean daily morphine milligram equivalents (MME). Differences among the three TCM Syndromes were analyzed by one-way ANOVA followed by Tukey post hoc testing. Two-sample t-tests were used to compare SCD and HC groups. TCM diagnosis criteria classified SCD patients into one of three TCM Syndromes: (a) Equal; (b) Deficiency; and (c) Stagnation. The Stagnation group exhibited higher pain interference, physical dysfunction, nociplastic pain, fatigue, anxiety, depression, MME consumption and lower sleep quality and QoL compared to the Equal group. Few differences were observed between HCs and the Equal SCD group across outcomes. Deficiency and Stagnation groups were differentiated with observed- and patient-reported clinical manifestations. These findings suggest that TCM diagnosed Syndromes in SCD can be differentially characterized using validated objective and patient-reported outcomes. Because characteristics of pain and co-morbidities in each SCD patient are unique, targeting specific TCM "Syndromes" may facilitate treatment effectiveness with a Syndrome-based personalized treatment plan that conforms to TCM principles. These findings lay the foundation for the development of tailored acupuncture interventions based on TCM Syndromes for managing pain in SCD. Larger samples are required to further refine and validate TCM diagnostic criteria for SCD.

The relationship of vitamin D levels with hemogram indices and metabolic parameters in patients with type 2 diabetes mellitus

<abstract><sec> <title>Background</title> <p>Vitamin D deficiency and Type 2 Diabetes (T2DM) are two important health problems that have rapidly increased prevalences in recent years. Chronic inflammation and susceptibility to infection are the characteristic features of T2DM. Vitamin D deficiency has been associated with high serum inflammatory marker levels due to its immunomodulatory effect. Moreover, studies have pointed out that vitamin D insufficiency could be associated with T2DM. Additionally, in recent years, inflammatory markers derived from hemogram have been associated with diabetes and its complications. Therefore, in our study, vitamin D levels, metabolic markers (i.e., serum uric acid, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol), and hemogram indices were analyzed in well controlled and poorly controlled T2DM patients. Furthermore, we compared those variables in vitamin D deficient and non-deficient groups.</p> </sec><sec> <title>Methods</title> <p>Laboratory data, including vitamin D and hemogram markers, were compared between poorly and well controlled T2DM patients who visited the outpatient internal medicine clinics of our institution.</p> </sec><sec> <title>Results</title> <p>A total of 240 T2DM individuals were included in the present study: 170 individuals had vitamin D deficiency and 70 individuals had normal vitamin D levels, who served as controls. The median neutrophil to lymphocyte ratio (NLR) value was 2.2 (0.74–7.4) in the vitamin D deficient group and 2.02 (0.73–5.56) in the vitamin D normal group (p = 0.025). Among the study parameters, the NLR and glycated hemoglobin (HbA1c) levels showed a significant positive correlation (r = 0.30, p < 0.001). The sensitivity and specificity of the NLR to predict vitamin D deficiency were determined as 60% and 49%, respectively (AUC: 0.59, p = 0.03, 95% CI: 0.51–0.67). The sensitivity and specificity of the NLR to predict an improved control of diabetes were 72% and 45%, respectively (AUC: 0.67, p < 0.001, 95% CI: 0.60–0.74).</p> </sec><sec> <title>Conclusions</title> <p>We think that NLR can be helpful in follow up of T2DM and vitamin D deficiency.</p> </sec></abstract>

Status of Vitamin B12 Deficiency among Lactating Mothers at Six Weeks Postpartum at a Tertiary Care Hospital, West Bengal, India

Introduction: Vitamin B12 (vit B12) deficiency is a preventable disorder and has dire consequences on the neurological development of the infant. The only source of vit B12 for exclusively breastfed newborns is their mother’s milk. So, determining the status of maternal vit B12 levels during early lactation is vital. In India, very few studies have documented vit B12 deficiency among lactating mothers, especially eastern region remains unexplored. Aim: To estimate the prevalence of vit B12 deficiency among healthy lactating mothers attending the postpartum clinic at six weeks at a Tertiary Care Hospital of West Bengal, India and also to compare the haematological values between vit B12 deficient and sufficient groups among the lactating mothers. Materials and Methods: An observational cross-sectional study was conducted in the Department of Biochemistry in collaboration with postpartum clinic of Calcutta National Medical College, West Bengal, India. The study was carried out over a period of two months, from July 2022 to August 2022. Serum vit B12, serum ferritin and haematological parameters {Haemoglobin (Hb), Mean Corpuscular Haemoglobin (MCH), Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin Concentration (MCHC)} were measured in 121 apparently healthy lactating women attending the postpartum clinic for a regular check-up at six weeks. Detailed socioclinical history and dietary history was taken from each participant and these variables were compared between vit B12 deficient and sufficient groups. Pearson’s Chi-square test, Fisher’s-exact test, Mann-Whitney U test were applied to analyse the data. Results: The total study population comprised of 121 mothers with an average age of 25.65±3.71 years and 75% of them consumed non vegetarian diet. A prevalence of 19 (15.7%) deficiency of vit B12 was found among the lactating mothers at six weeks postpartum. Mothers who were vegetarian, multigravida and with complaints of paraesthesia were more associated to cobalamin deficiency. The vit B12 deficient mothers had significantly higher erythrocyte indices than the sufficient group but none of the values were in the megaloblastic range. Conclusion: The vit B12 deficiency was prevalent during early lactation in 19 (15.7%) lactating mothers. The first postnatal visit at six weeks might be the most feasible period to screen and supplement these women to prevent long term sequelae in both mother and child. Haematological parameters were of limited use in identifying vit B12 deficiency during lactation.

Vitamin D Status of Children Attending the Well Child Clinic of a Private Hospital in Yangon

Introduction: Vitamin D is essential for the healthy development and maintenance of bones, particularly in childhood and adolescence. We aimed to figure out the vitamin D concentrations among children who were 4 to 15 years and came to health check-up clinics of a private hospital in Yangon. Methods: This is a retrospective record review study over 1 year which included a total of 99 well children aged 4 to15 years. We collected demographic and clinical details as well as blood samples including (25 (OH) D and alkaline phosphatase. For statistical analysis, we applied IBM SPSS 25.0. Results: Among 99 participants, 43 (43.4%) were found to have vitamin D deficiency. The average serum 25 (OH) D level among all subjects was 21.77±7.03 ng/mL, while those with deficiency had an average level of 15.53±3.32 ng/mL. Notably, a higher percentage of obese children, 10 out of 16 (62.5%) were affected with vitamin D deficiency. There was a statistically significant age difference between the vitamin D deficient group (mean age 10.07±3.16 years) and their sufficient counterparts (mean age 7.70±2.71 years). Conclusions: A significant incidence of vitamin D deficiency was detected among healthy children. It appears to escalate with age, implying an inverse relationship between age and vitamin D levels. The association between low serum 25 (OH) D and obesity in children underscores the significance of dietary pattern, lifestyle modification, and sunlight exposure in attaining optimal vitamin D levels. These measures may lessen the risk of multiple disease states related to low vitamin D.

Lower levels of vitamin D are associated with an increase in carotid intima-media thickness in children and adolescents with obesity.

the relationship between vitamin D deficiency and carotid intima-media thickness (CIMT) in children and adolescents with obesity is unknown. The aim of this study was to investigate the correlation between vitamin D levels and CIMT in children and adolescents with obesity. a total of 440 children and adolescents aged 6-16 with obesity were included in the study. Anthropometric measurements, blood pressure measurements, blood lipids, blood glucose, and vitamin D levels were measured. Bilateral carotid ultrasound was performed to assess CIMT. The relationships between vitamin D levels and CIMT were assessed using multivariate linear regression with Generalized Linear Models and restricted cubic splines. Binary logistic regression analyses were conducted to explore the association between vitamin D status and the risk of abnormal CIMT. vitamin D levels were inversely correlated with CIMT in subjects with serum 25-hydroxyvitamin D [25(OH)D] levels less than or equal to 50 nmol/L (ß = -0.147, 95 % CI [-0.263, -0.030], p = 0.013), but this correlation was not significant in subjects with serum 25(OH)D levels above 50 nmol/L. After correcting for various confounders, the risk of abnormal CIMT was significantly higher in the vitamin D deficiency group (OR = 2.080, 95 % CI [1.112, 3.891], p = 0.022). vitamin D deficiency is an independent risk factor for abnormal CIMT, and vitamin D deficiency may play a promoting role in the atherosclerotic process in children and adolescents with obesity.

Correlation between serum 25-hydroxyvitamin D level and peripheral arterial disease in patients with type 2 diabetes mellitus: a single-center retrospective study.

To investigate the association between serum 25-hydroxyvitamin D (25(OH)D) level and peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). This retrospective study analyzed data from 752 T2DM patients treated at Shaoyang Central Hospital between September 2020 and September 2023. Patients were divided into two groups: those with T2DM alone and those with T2DM and PAD. We compared demographic data, biochemical indices, and ankle-brachial index (ABI) values. Pearson correlation and multivariate logistic regression with a forward likelihood ratio method assessed the relationship and risk factors. The predictive value of serum 25(OH)D levels for PAD was evaluated using receiver operating characteristic (ROC) analysis. The T2DM+PAD group was older and had a longer duration of diabetes compared to the T2DM group. This group also had lower BMI, diastolic blood pressure, and ABI values, but higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) (all P<0.05). Serum 25(OH)D levels were significantly lower in the T2DM+PAD group (P<0.05). ABI negatively correlated with age, diabetes duration, LDL-C, and TC, and positively with BMI and 25(OH)D levels (all P<0.05). Older age, lower BMI, higher LDL-C, and lower 25(OH)D levels were independent risk factors for PAD (ORs: 1.060, 0.781, 1.083, and 0.959, respectively; all P<0.05). The risk of PAD was significantly higher in the 25(OH)D deficiency group (P<0.05). The AUC for serum 25(OH)D in predicting PAD occurrence was 0.629. Lower serum 25(OH)D levels are associated with higher risk of PAD in patients with T2DM. Early identification and management of 25(OH)D deficiency may be crucial for preventing PAD in this population.

Obstacles to Inclusive Disability Hate Crime Policy Process: Targeting the Cognitively Impaired Elderly Victim Group

In England and Wales, Section 146 of the Criminal Justice Act 2003 made disability hate crimes legal. This advocated for increased sentencing for perpetrators whose crimes were motivated by or demonstrated hate against a person with a handicap or a perceived disability. Currently, this additional sentencing provision is the only legal option for prosecuting disability hate crime perpetrators. This thesis explores the experience and aftermath of hate crimes committed against England’s cognitively challenged senior victim group. The cognitively challenged elderly victim group is far more likely to face bias and violence; they have a greater likelihood of re-victimisation and suffer significant suffering as a result of hate crimes. To date, the voices of cognitively deficient elderly victims and survivors have been mostly absent from scholarly research and hate crime policies. As a result, the purpose of this article is to look into present policy barriers and how the cognitively challenged senior victim group might best receive support, justice, and interventions following discriminatory hate crimes. There has been little examination and discussion of intersectionality in disability studies and hate crime research. Common ideas fail to adequately reflect the multifaceted, overlapping, and complex experiences of danger and victimisation. This paper builds on studies on hate crimes against the cognitively deficient elderly victim group. It noted the challenge of categorising individual encounters as one type of hate crime. Victims and their relatives recognised that they were targeted for a variety of reasons, including their inability to care for themselves and their age. The study contends that the present strand-based approach to hate crime conceals a multitude of cross-identity characteristics that, when combined, might raise the danger of victimisation while decreasing a victim’s chance of reporting their experiences. To address vulnerability, safety, and hate crime against disabled people in England and Wales’ criminal justice, health, social care, and refuge systems, barriers to including the cognitively impaired senior victim group in the policy process are presented, allowing for targeted suggestions and changes on relevant issues.

The Cdc42/Rac1 pathway: a molecular mechanism behind iron-deficiency-driven aortic medial degeneration.

To elucidate the underlying mechanism of iron deficiency augmented Angiotensin II-induced aortic medial degeneration. ApoE-/- mice were randomly divided into four groups: normal control group (NC group), Angiotensin II (Ang II) subcutaneous pumped alone Group (Ang II group), iron deficiency (ID) group (ID group) and ID+Ang II group. The survival time, systolic blood pressure (SBP), and aortic medial degeneration (AMD) formation were monitored. Iron deposition in the aortas was assessed using Prussian blue iron staining. The expression of iron metabolism indicators, aortopathies and the cytoskeleton of vascular smooth muscle cells (VSMCs) were analyzed. In an in vitro setting, deferoxamine (DFO) was employed to mimic ID to examine the effects of Ang II on the cytoskeletal and contractile function of VSMCs during ID. Ras-related C3 botulinum toxin substrate 1 (Rac-1) expression was inhibited with EHT1864 to verify the role of Cdc42/Rac1 pathway in this pathological process. Blood samples were collected from 150 patients with aortic dissection (AD) and 60 patients with hypertension who were admitted to the Department of Cardiovascular Surgery at Renmin Hospital of Wuhan University between June 2018 and September 2019. The aortic tissues were obtained during the surgical treatment of Stanford type A AD patients and the heart donor. The iron metabolism status in plasma and aortic tissue was analyzed. In vivo experiments revealed that, in comparison to the NC and ID groups, mice in the Ang II and ID+Ang II groups exhibited increased SBP, significantly reduced survival time, and an expanded range of aortic dissection (P < 0.05). ID feeding augmented the Ang II-induced aortopathies. Both in vitro and in vivo results indicated that ID led to diminished expression of phosphorylated myosin light chain (p-MLC) and recombinant Cell Division Cycle Protein 42 (Cdc42) in VSMCs, while Rac-1 expression increased. The clinical sample testing data further confirmed the discovery that individuals diagnosed with AD display ID in both the plasma and the diseased aortas. The Cdc42/Rac1 pathway plays a crucial role in disrupting the cytoskeleton of vascular smooth muscle cells during iron deficiency, which leads to aortic medial degeneration both in vivo and in vitro.

The association between serum vitamin A concentrations and virus hepatitis among U.S. adults from the NHANES database: a cross-sectional study.

According to the present study, the relationship between vitamin A (VA) levels and hepatitis virus carriage has been unclear and controversial. This study aimed to determine the potential relationship between serum VA levels and viral hepatitis and to provide ideas for future clinical treatments. A cross-sectional study was performed using the 2005-2006 and 2017-2018 National Health and Nutrition Examination Survey (NHANES) datasets. Multiple linear regression and logistic regression were adopted to analyze the association between serological hepatitis B surface antigen (HBsAg) or hepatitis C RNA (HCV-RNA) positivity and VA levels. There were 5,351 HBsAg-related responders and 242 HCV-RNA-related responders, including 52 HBsAg (+) and 104 HCV-RNA (+) responders. Compared with HBsAg (-) and HCV-RNA (-) respondents, HBsAg (+) and HCV-RNA (+) respondents tended to have lower serum VA levels, respectively [1.63 (1.33 ~ 2.01) vs. 1.92 (1.57 ~ 2.34), P < 0.001; 1.54 (1.25 ~ 1.83) vs. 1.78 (1.46 ~ 2.26), P < 0.001]. A greater percentage of responders in the subclinical VA deficiency (SVAD) group were HBsAg (+) and HCV-RNA (+) than were those in the normal VA (VAN) group [2.4% (9/374) vs. 0.9% (43/4977), p = 0.003; 61.5% (16/26) vs. 40.7% (88/215), p = 0.043]. According to the results of the multiple regression analyses of the different models, the serum VA concentration was negatively correlated with HBsAg (+) and HCV-RNA (+) status (β = -0.14, 95% CI = -0.30 to -0.01, p = 0.066; β = -0.29, 95% CI = -0.50 ~ -0.09, p = 0.005, respectively). Compared to those with SVAD, patients with VAN were less likely to be serologically HBsAg (+) or HCV-RNA (+) (OR = 0.53, 95% CI = 0.25 ~ 1.10, p = 0.089; OR = 0.39, 95% CI = 0.18 ~ 0.84, p = 0.016, respectively). Our study provides evidence that patients who are HBsAg (+) or HCV-RNA (+) have a high incidence of SVAD. Moreover, HBsAg and HCV-RNA positivity are negatively correlated with VA levels, and patients with SVAD are more likely to carry HBsAg (+) or HCV-RNA (+). These findings suggest that the relationship between hepatitis viruses and vitamin A needs to be validated by more basic studies and clinical large-sample randomized controlled trials to provide ideas for new therapeutic targets.

Association of HbA1c Variability with Vibrating Perception Threshold in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

To investigate the relationship between HbA1c variability and vibrating perception threshold (VPT) in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). A total of 367 middle-aged and elderly patients with T2DM were enrolled. All patients were categorized into the control and vibration sensation deficiency group (VSD) based on VPT. Clinical data were collected. The coefficient of variation of glycated hemoglobin A1c (HbA1c-CV) and the mean glycated hemoglobin A1c(HbA1c-Mean) are considered as indexes of HbA1c variability. Multivariate logistic regression analysis, the generalized linear model and ROC curve correlation analysis were used to analyze the correlation of various factors and VPT. The multivariate logistic regression analysis revealed that age, systolic blood pressure (SBP), and HbA1c-CV were identified as risk factors for vibration sensation deficiency in middle-aged and elderly patients with T2DM, while estimated glomerular filtration rate (eGFR), triiodothyronine (T3), and alanine aminotransferase (ALT) were considered as protective factors. In the unadjusted generalized linear model, a significant association was observed between HbA1c-CV and VPT values. After adjusting for age, diabetic duration, SBP, homeostatic model assessment for beta-cell function (HOMA-β), ALT, eGFR, T3, 24-hour urinary protein excretion levels, and HbA1c-Mean, HbA1c-CV remained significantly correlated with VPT values on both sides. (left side, B=2.560, 95% CI 1.298~3.823; P<0.001; right side, B=2.608, 95% CI 1.498~3.718, P<0.001). The area under the curve (AUC) for HbA1c-CV and VSD prevalence was 0.723, with a sensitivity of 79.85%, specificity of 56.22%. The risk of developing VSD increases proportionally with higher HbA1c-CV levels in middle-aged and elderly patients with T2DM. Reaching and maintaining blood glucose stability is essential to the mitigation of diabetes peripheral neuropathy occurrence.

Biotinidase biochemical and molecular analyses: Experience at a large reference laboratory.

Biotinidase deficiency is caused by absent activity of the biotinidase, encoded by the biotinidase gene (BTD). Affected individuals cannot recycle the biotin, leading to heterogeneous symptoms that are primarily neurological and cutaneous. Early treatment with biotin supplementation can prevent irreversible neurological damage and is recommended for patients with profound deficiency, defined as enzyme activity <10% mean normal (MN). Molecular testing has been utilized along with biochemical analysis for diagnosis and management. In this study, our objective was to correlate biochemical phenotype/enzyme activity to BTD genotype in patients for whom both enzyme and molecular testing were performed at our lab, and to review how the correlations inform on variant severity. We analyzed results of biotinidase enzyme analysis and BTD gene sequencing in 407 patients where samples were submitted to our laboratory from 2008 to 2020. We identified 84 BTD variants; the most common was c.1330G>C, and 19/84 were novel BTD variants. A total of 36 patients had enzyme activity <10% of MN and the most common variant found in this group was c.528G>T. No variant was reported in one patient in the profound deficiency group. The most common variant found in patients with enzyme activity more than 10% MN was c.1330G>C. Although enzyme activity alone may be adequate for diagnosing profound biotinidase deficiency, molecular testing is necessary for accurate carrier screening and in cases where the enzyme activity falls in the range where partial deficiency and carrier status cannot be discriminated.

Sensitive monitoring of NAD(P)H levels within cancer cells using mitochondria-targeted near-infrared cyanine dyes with optimized electron-withdrawing acceptors.

A series of near-infrared fluorescent probes, labeled A to E, were developed by combining electron-rich thiophene and 3,4-ethylenedioxythiophene bridges with 3-quinolinium and various electron deficient groups, enabling the sensing of NAD(P)H. Probes A and B exhibit absorptions and emissions in the near-infrared range, offering advantages such as minimal interference from autofluorescence, negligible photo impairment in cells and tissues, and exceptional tissue penetration. These probes show negligible fluorescence when NADH is not present, and their absorption maxima are at 438 nm and 470 nm, respectively. In contrast, probes C-E feature absorption maxima at 450, 334 and 581 nm, respectively. Added NADH triggers the transformation of the electron-deficient 3-quinolinium units into electron-rich 1,4-dihydroquinoline units resulting in fluorescence responses which were established at 748, 730, 575, 625 and 661 for probes AH-EH, respectively, at detection limits of 0.15 μM and 0.07 μM for probes A and B, respectively. Optimized geometries based on theoretical calculations reveal non-planar geometries for probes A-E due to twisting of the 3-quinolinium and benzothiazolium units bonded to the central thiophene group, which all attain planarity upon addition of hydride resulting in absorption and fluorescence in the near-IR region for probes AH and BH in contrast to probes CH-EH which depict fluorescence in the visible range. Probe A has been successfully employed to monitor NAD(P)H levels in glycolysis and specific mitochondrial targeting. Furthermore, it has been used to assess the influence of lactate and pyruvate on the levels of NAD(P)H, to explore how hypoxia in cancer cells can elevate levels of NAD(P)H, and to visualize changes in levels of NAD(P)H under hypoxic conditions with CoCl2 treatment. Additionally, probe A has facilitated the examination of the potential impact of chemotherapy drugs, namely gemcitabine, camptothecin, and cisplatin, on metabolic processes and energy generation within cancer cells by affecting NAD(P)H levels. Treatment of A549 cancer cells with these drugs has been shown to increase NAD(P)H levels, which may contribute to their anticancer effects ultimately leading to programmed cell death or apoptosis. Moreover, probe A has been successfully employed in monitoring NAD(P)H level changes in D. melanogaster larvae treated with cisplatin.

A deep-red xanthene-based highly sensitive fluorescent probe for detection of hypochlorite.

As an oxidant, deodorant and bleaching agent, the hypochlorous acid (HClO) and hypochlorite (ClO- ) are widely used in corrosion inhibitors, textile dyes, pharmaceutical intermediates and in our daily lives. However, excess usage or aberrant accumulation of ClO- leads to tissue damage or some diseases and even cancer. Therefore, it is necessary to develop a fluorescent probe that specifically identifies ClO- . In this article, we synthesized a deep-red xanthene-based fluorescent probe (XA-CN). The strong electron deficient group dicyano endows the probe XA-CN deep-red fluorescent emission with high solubility, selectivity and sensitivity for ClO- detection. Studies showed that the probe demonstrated turn-off fluorescence (643 nm) at the presence of ClO- in dimethylsulfoxide/phosphate-buffered saline 1:1 (pH9) solution with a limit of detection of 1.64 μM. Detection mechanism investigation revealed that the electron deficient group -CN and the hydroxyl group was oxidized into aldehyde or carbonyl groups at the presence of ClO- , resulting ultraviolet-visible absorption of the probe blue shifted and turned-off fluorescence. Furthermore, XA-CN was successfully used for the detection of ClO- in tap water samples.

Serum 25-hydroxyvitamin D concentrations and their impact on all-cause mortality in Parkinson's disease: insights from National Health and Nutrition Examination Survey 1999-2020 data.

This study explores the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and mortality among Parkinson's disease (PD) patients, providing evidence for the potential benefits of vitamin D (VD) supplementation. PD patients were collected from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2020. These patients were categorized based on their serum 25(OH)D levels: deficiency, insufficiency, and sufficiency. We compared demographic information and analyzed mortality data from the National Death Index. A restricted cubic spline model assessed the nonlinear association between 25(OH)D levels and mortality, complemented by multivariable Cox regression analysis. Consistency of results was checked through subgroup analysis. The study included 364 PD patients: 87 (23.9%) with VD deficiency, 121 (33.2%) with insufficiency, and 156 (42.9%) with sufficiency. Demographically, 46.4% were male, and 56% were over 65 years. The deficiency group predominantly consisted of Mexican Americans (53.1%), had lower income levels, a higher unmarried rate, and increased liver disease incidence. The analysis showed a U-shaped curve between 25(OH)D levels and mortality risk, with the lowest risk at 78.68 nmol/L (p-non-linear = 0.007, p-overall = 0.008). Kaplan-Meier analysis found the highest survival rates in patients with 25(OH)D levels between 75-100 nmol/L (p = 0.039). Compared to this group, patients with levels below 50 nmol/L had a 3.52-fold increased mortality risk (95% CI = 1.58-7.86, p = 0.002), and those above 100 nmol/L had a 2.92-fold increase (95% CI = 1.06-8.05, p = 0.038). Age-specific subgroup analysis (p = 0.009) revealed that both very low (<50 nmol/L) and high (>100 nmol/L) levels increased mortality risk in patients under 65, while levels below 75 nmol/L raised mortality risk in older patients. Serum 25(OH)D levels are nonlinearly linked to mortality in PD patients, with optimal survival rates occurring at 75-100 nmol/L. Deviations from this range increase the risk of death.

Selenium Deficiency Can Promote the Expression of VEGF and Inflammatory Factors in Cartilage Differentiation and Mediates Cartilage Injury.

Selenium plays a crucial role as a micronutrient, primarily exerting its biological functions through selenoproteins. It has been established that selenium deficiency adversely impacts cartilage development, leading to alterations in chondrocyte function. In regions with low selenium intake, endemic osteochondrosis has been documented, characterized by compromised growth plate and articular cartilage formation. Vascular endothelial growth factor (VEGF) stands out as a pivotal angiogenic factor, with elevated levels contributing significantly to vascular invasion into chondrocytes. This VEGF-mediated invasion serves as a key signal, prompting morphological changes in the growth plate and initiating cartilage remodeling. In animal models, the selenium deficiency group exhibited heightened levels of the cartilage damage marker matrix metalloproteinases 13 (MMP13). This resulted in articular cartilage degeneration, accompanied by a substantial increase in VEGF expression within the growth plate and articular cartilage, as compared to the normal group. In a chondrogenic progenitor cell (CPC) differentiation model, insufficient selenium induced chondrocyte damage and upregulated inflammatory factors such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX2). The selenium-deficient groups showed elevated expressions of VEGF, VEGFR2, MMP13, Collagen X, and Angiopoietin 1, accelerating the degradation of the extracellular matrix (ECM), which further promoted the development of cartilage-related diseases. Taken together, these findings provide novel insights for a better understanding of the role of low selenium in cartilage degeneration and angiogenesis. They shed light on the intricate influence of low selenium levels on the development of articular cartilage, emphasizing the interconnected pathways and processes involved.

Effects of Dietary Zinc Deficiency and Supplementation on Prepubertal Rat Testes: Sulfhydryl and Antioxidant Status.

The study was designed to investigate the effects of dietary zinc deficiency and supplementation on antioxidant system viz. superoxide-dismutase, glutathione reductase, glutathione peroxidase, glutathione- S-transferase, catalase and sulfhydryls levels (GSH, TSH, NPSH and PBSH) in testes of Wistar rats. Pre-pubertal rats were divided into two groups with 6 sub-groups each viz. zinc control (ZC), pair fed (PF), zinc deficient (ZD), zinc control supplementation (ZCS), pair-fed supplementation (PFS) and zinc deficient supplementation (ZDS). Experiments were set for 2- and 4-weeks followed by 4weeks of zinc supplementation. The zinc deficient group animals exhibited significant decrease in gonado-somatic index (2- and 4- weeks), sulfhydryls levels, GSH, GPx, GR (2 and 4-weeks) and GST concentration (2-weeks). However, after zinc supplementation significant improvement in gonadosomatic index, SH, GSH, antioxidant enzyme levels (GR, GPx, and GST) in deficient groups has been observed. Zinc deficiency during pre-pubertal period affected growth and caused dysregulation of the glutathione antioxidant system. The significant alterations in the levels of antioxidant enzymes and non-enzymatic antioxidant system (GSH and SH) in zinc deficient groups could be due to alleviated generation of free radicals, causative factor for increased oxidative stress which may lead to infertility as oxidative stress is a common pathology seen during infertility. Altered antioxidant system and sulfhydryls levels in testes due to dietary zinc deficiency reflect the significance of optimum zinc for maintaining homeostatic balance in gonadal physiology. Supplementing zinc for 4weeks could reduce the redox imbalance which may help in alleviating oxidative stress induced alterations in testes.

Lower extremity arterial plaque in patients with type 2 diabetes mellitus: A cross-sectional study of 25-(OH)D3 and other risk factors

ObjectiveThe occurrence of chronic vascular complications in individuals with type 2 diabetes mellitus(T2DM) is influenced by multiple factors. This study aims to analyze the correlation between serum 25-(OH)D3 levels and other risk factors with the formation and severity of arterial plaques in the lower extremities, and explore its role in clinical diagnosis and treatment. MethodsA total of 628 Chinese patients with T2DM were included in this study. Based on the intima-media thickness (IMT) and plaque echogenicity measured by lower extremity vascular ultrasound, the patients were divided into the no plaque group(NP), low-risk plague group(LP), moderate-risk plague group(MP), and severe-risk plague group(SP). Based on 25-(OH)D3 levels, patients were categorized as vitamin D deficient group (VDD，25-(OH)D3 ≤ 20 ng/mL), vitamin D insufficient group (VDI，25-(OH)D3 between>20 ng/mL and < 30 ng/mL), and vitamin D sufficient group (VDS，25-(OH)D3 ≥ 30 ng/mL). The correlation between the severity of lower extremity arterial plaques and serum 25-(OH)D3 levels was analyzed, as well as the risk factors for lower extremity arterial plaque formation in patients with T2DM. ResultsThe levels of 25-(OH)D3 in patients with arterial plaques were significantly lower than those in the NP (p = 0.002). Additionally, with the increasing severity of lower extremity arterial plaques, 25-(OH)D3 levels also decreased significantly (p = 0.01). The proportion of patients with sufficient 25-(OH)D3 levels was highest in NP, while the proportion of deficient and insufficient groups was higher in LP (p<0.001). Multivariate logistic regression analysis showed that low levels of 25-(OH)D3 were an independent risk factor for lower extremity arterial plaques in T2DM patients. Compared to patients with 25-(OH)D3>20 ng/mL, the odds ratios for the formation of moderate-risk plaques were 2.525 (95 % CI: 1.45–4.39) in patients with 25-(OH)D3 ≤ 20 ng/mL, and 2.893 (95 % CI: 1.59–5.26) for the formation of high-risk plaques. ConclusionSerum 25-(OH)D3 levels may be correlated with the occurrence and severity of lower extremity arterial plaques in patients with T2DM. Low serum 25-(OH)D3 concentration is a risk factor for lower extremity vascular lesions.

The Association between Serum 25-Hydroxyvitamin D3 Levels and Pro-Inflammatory Markers in New-Onset Type 2 Diabetes Mellitus and Prediabetes.

In this study, we aimed to reveal the pro-inflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabetes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy participants. We measured the levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in the serum of the participants. ANOVA Bonferroni and Kruskal-Wallis Dunn tests were used to compare the inflammation markers and vitamin D levels between the groups. Based on covariance analysis with age, gender and BMI, the Vit D levels of the T2DM group were significantly lower (p < 0.003). Pro-inflammatory markers and CRP were significantly higher in prediabetic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In the T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the pro-inflammatory effects of Vit D deficiency and insufficiency in new-onset type 2 diabetes mellitus and prediabetes.

The influence of zinc on apoptosis and cell proliferation in palatal shelves during the fusion phase in mice and identification of a special protein family based on gene expression in cleft palate

Objective: To investigate the effect of the trace element zinc (Zn) on apoptosis and cell proliferation in palate shelvesduring the fusion phase, and to screen candidate genes of the Zn-finger special protein (Sp) family that were differentially expressed between the cleft palate and the normal palate to explore the mechanism of Zn in the development of cleft palate. Methods: Zn-rich, normal-Zn, low-Zn, and Zn-deficient diets were fed to female mice and, for the resultant fetuses, paraffin slices of their heads were made at embryonicdays 14.5 and 16.5. Using terminaldeoxynucleotidyltransferase-mediated dUTP nick-end labeling, the number of apoptotic cells in the palatal shelves was counted, and cell proliferation activity was detected using proliferating cell nuclear antigen staining. Total RNA from the palatal shelves of fetal mice was extracted from the Zn-rich diet, normal Zn-diet, and Zn-deficient-diet groups. We used microarray analysis to examine the expression of genes to identify intergroup differential gene expression and polymerase chain reaction tests to validate the results. Results: At ED14.5, the incidence of cleft palate in the regular zinc group, zinc rich group, low zinc group, and zinc deficient group was 8% (3/36), 2% (1/39), 29% (12/41), and 39% (15/38), respectively. The HE staining results at ED14.5 showed that both the left and right palatal processes in the zinc group had been lifted up and were in contact and connected with each other. In the zinc deficiency group, the left and right palatine processes remained vertically downwards on both sides of the tongue, ultimately forming cleft palate; In the low zinc group, the left and right palatine processes were raised but not in contact, ultimately resulting in cleft palate. There is no significant difference between the zinc rich group and the regular zinc group. At ED14.5, the positive rates of proliferative cells in the palatal process of fetal mice in the regular zinc group (80.29% ± 7.39%) and the zinc rich group (87.69% ± 6.62%) were significantly higher than those in the zinc deficient group (56.05% ± 16.13%) and the low zinc group (56.22% ± 9.61%) (t=4.32, P<0.05). The apoptosis index of fetal rat palatal process cells in the zinc deficient group (38.80% ± 3.10%) and the low zinc group (28.80% ± 6.19%) were significantly higher than those in the regular zinc group (16.80% ± 1.82%) (t=19.35, P<0.001; t=5.81, P<0.001). There were 663 differentially expressed genes in the zinc rich group and the zinc deficient group, with 513 up-regulated genes and 150 down-regulated genes, among which Sp5 was found to be located. The real time PCR results showed that compared with the regular zinc group (2.22 ± 0.36), the expression level of Sp5mRNA in the palatal process tissue of the zinc deficient group (1.23 ± 0.38) significantly increased (P<0.05), while the zinc rich group (3.68 ± 0.90) significantly decreased (P<0.05). Conclusions: Trace element Zn content was found to be closely related to the occurrence of cleft palate in mice offspring, with a lack of Zn leading to cleft palate.