The predictive value of TyG and lipid ratios on the development of complications and hyperuricemia in patients with type 2 diabetes mellitus.

Investigate the predictive value of TyG and lipid ratios on the development of complications and HUA in patients with T2DM. A retrospective cross-sectional study involving 9488 T2DM patients was conducted. They were divided into HUA and NUA group base on SUA level and divided into with and without complications groups according to the diagnosis of the endocrinologist. Necessary information and biochemical parameters were recorded during outpatient visit. TyG index and lipid ratios were calculated, and statistical analysis was carried out to correlate the calculated values and HUA using SPSS version 26.0 for Windows. TyG and lipid ratios were significantly higher in T2DM with HUA or with complications than those with NUA or without complications (p < 0.05). Regression analysis adjusting for confounding factors found TyG (adjusted OR = 1.54; 95% CI: 1.31-1.82; p < 0.05), TG/HDL-C (adjusted OR = 1.21; 95% CI: 1.04-1.40; p < 0.05) and TC/HDL (adjusted OR = 1.36; 95% CI: 1.17-1.57; p < 0.05) was risk factor of HUA in T2DM patients. TyG (adjusted OR = 1.21; 95% CI: 1.02-1.44; p < 0.05), TG/HDL (adjusted OR = 1.19; 95% CI: 1.03-1.38; p < 0.05) and Apo A/Apo B (adjusted OR = 1.41; 95% CI: 1.26-1.58; p < 0.05) was risk factor of complications in T2DM patients. TyG, TG/HDL-C, and TC/HDL can be used as early sensitive target in the occurrence of HUA in T2DM patients and TyG was the most influential risk factor. TyG, TG/HDL-C, and Apo A/Apo B can be used as early sensitive target in the occurrence of complications in T2DM patients and Apo A/Apo B was the most influential risk factor.

Cardiovascular mortality in people with cancer compared to the general population: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of non-cancer death in cancer survivors, but the risk of CVD varies between cancers. OBJECTIVES: To synthesise available evidence on patterns and magnitude of CVD mortality risk. METHODS: A systematic search of Medline (OVID), CINAHL and Scopus databases from 01-January-2000 to 16-July-2023 of studies of people with cancer, reporting CVD mortality in cancer population compared with a reference population (e.g. general population) as standardised mortality ratios (SMR). Meta-analysis of SMRs across cancer and CVD types were pooled using a random-effects model to allow for heterogeneity of the true effect size across studies. RESULTS: We identified 136 studies from 16 countries. Sample sizes ranged from 157 to 7,529,481. The majority (n = 98; 72%) were conducted in the United States, followed by Europe (n = 22; 16%). The most common cancers studied were gastrointestinal (n = 34 studies), haematological (n = 31) and breast (n = 29). A total of 876 CVD SMRs were extracted across diverse CVD conditions. Of those, the majority (535; 61%) indicated an increased risk of CVD death (SMR >1), 109 (12%) a lower risk of CVD death (SMR <1) and 232 (27%) an equivalent risk (95% CI of SMR included 1) compared to the general population. The meta-analysis of all reported SMRs showed an increased risk of CVD death (SMR = 1.55, 95% CI = 1.40-1.72) in cancer survivors compared with the general population. The SMR varied between CVD conditions and ranged from 1.36 (95% CI = 1.29-1.44) for heart diseases to 1.56 (95% CI = 1.39-1.76) for cerebrovascular diseases. SMR varied across cancer types, ranging from 1.14 (95% CI = 1.04-1.25) for testicular/germ cell tumours to 2.82 (95% CI = 2.20-3.63) for brain/central nervous system tumours. CONCLUSIONS: Cancer survivors are at increased risk of premature CVD mortality compared to the general population, but the risk varies by cancer type and CVD. Future research should focus on understanding mechanisms behind the increased CVD risk to develop appropriate interventions.

The impact of PM2.5 and its constituents on gestational diabetes mellitus: a retrospective cohort study.

BACKGROUND: There is increasing evidence that exposure to PM2.5 and its constituents is associated with an increased risk of gestational diabetes mellitus (GDM), but studies on the relationship between exposure to PM2.5 constituents and the risk of GDM are still limited. METHODS: A total of 17,855 pregnant women in Guangzhou were recruited for this retrospective cohort study, and the time-varying average concentration method was used to estimate individual exposure to PM2.5 and its constituents during pregnancy. Logistic regression was used to assess the relationship between exposure to PM2.5 and its constituents and the risk of GDM, and the expected inflection point between exposure to PM2.5 and its constituents and the risk of GDM was estimated using logistic regression combined with restricted cubic spline curves. Stratified analyses and interaction tests were performed. RESULTS: After adjustment for confounders, exposure to PM2.5 and its constituents (NO3-, NH4+, and OM) was positively associated with the risk of GDM during pregnancy, especially when exposure to NO3- and NH4+ occurred in the first to second trimester, with each interquartile range increase the risk of GDM by 20.2% (95% CI: 1.118-1.293) and 18.2% (95% CI. 1.107-1.263), respectively. The lowest inflection points between PM2.5, SO42-, NO3-, NH4+, OM, and BC concentrations and GDM risk throughout the gestation period were 18.96, 5.80, 3.22, 2.67, 4.77 and 0.97 µg/m3, respectively. In the first trimester, an age interaction effect between exposure to SO42-, OM, and BC and the risk of GDM was observed. CONCLUSIONS: This study demonstrates a positive association between exposure to PM2.5 and its constituents and the risk of GDM. Specifically, exposure to NO3-, NH4+, and OM was particularly associated with an increased risk of GDM. The present study contributes to a better understanding of the effects of exposure to PM2.5 and its constituents on the risk of GDM.

Understanding air pollution reduction from the perspective of synergy with carbon mitigation in China from 2008 to 2017.

In response to the dual challenges of air pollution control and carbon mitigation, China has strategically shifted its focus towards the synergistic reduction of air pollutants and CO2 emissions. This study identifies the potential areas and specific air pollutant species (including CO, NOx, and SO2) for co-reduction with carbon mitigation. We also reveal the driving forces behind the emissions of each air pollutant at both the national and regional scales. Our findings are as follows: (1) The potential for synergistic reduction of CO and SO2 with CO2 emissions has diminished in economically developed areas. There is a significant opportunity for co-reduction of SO2 and CO2 in the western and northern regions of China, particularly within Heilongjiang Province. (2) NOx is the key species for synergistic reduction with CO2 emissions across China, especially in the Chengyu Plain. (3) Cleaner production and the synergistic reduction effect are the primary contributors to national air pollutant reduction in China from 2008 to 2017. Conversely, efforts in economic development and energy efficiency have led to emission increases. Energy and industrial structures have only made limited contributions to emission reductions, and carbon mitigation shows an inhibition effect on emission reductions. These results offer valuable insights for developing targeted regional strategies for deeper air pollution control, considering the specific characteristics and needs of each region. Additionally, our findings highlight the importance of addressing policy misalignments and strengthening mutual-influence mechanisms between air pollution control and carbon mitigation, ensuring that policies for carbon reduction also effectively contribute to air quality improvements.

Radiological abnormalities of the cervicothoracic vertebrae in Warmblood horses with primary neck-related clinical signs versus controls.

Radiological observations at the cervicothoracic junction in horses with or without related clinical signs have not been comprehensively described. The aim was to evaluate the seventh cervical (C7) to second thoracic (T2) vertebrae in horses with neck-related clinical signs (neck pain and/or stiffness, neck-related forelimb lameness, or general proprioceptive [spinal] ataxia) and control horses. This prospective analytical cross-sectional study included 127 control horses and 96 cases, examined using standardized clinical and radiological protocols. Univariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify factors associated with radiological abnormalities. Severe modeling of the articular processes at C7-T1 was more likely in cases compared with controls, OR, 4.25; CI, 1.04-17.36; P = .04. Cases were more likely to have spondylolisthesis at C7-T1 than controls, OR, 3.61; CI, 1.75-7.44; P < .001. There was a lack of uniformity of disc space width at C6-C7, despite normal alignment of the vertebrae, in five (5.2%) cases and no control horses. Discospondylosis was seen in 9 (9.4%) horses at C7-T1 and 10 of 64 (15.6%) at T1-T2. The sagittal ratio for T1 was smaller for horses with neck-related forelimb lameness (P < .0002), neck pain/ stiffness (P = .04), or neurological cases (P < .001) than controls. The prevalence of radiological abnormalities at C7-T1 and T1-T2 highlights the importance of careful evaluation of the cervicothoracic junction in horses with neck-related signs.

Mitochondria from the systemic heart of Pacific hagfish (Eptatretus stoutii) are insensitive to one hour of anoxia followed by reoxygenation.

Pacific hagfish (Eptatretus stoutii) are an ancient agnathan vertebrate known to be anoxia tolerant. To study their metabolic organization and the role of the mitochondria in anoxia tolerance we developed a novel protocol to measure mitochondrial function in permeabilized cardiomyocytes and how this is affected by one hour of anoxia followed by reoxygenation. When measured at 10 °C the mitochondria had a respiration rate of 2.1 ± 0.1pmol/s/mg WW during OXPHOS with saturating concentrations of glutamate, malate, and succinate. This is comparatively low compared to other ectothermic species. The functional characteristics of the mitochondria were quantified with mitochondrial control ratios. These demonstrated that proton leak contributed to just under 50% of the oxygen flux, with the remainder going towards ATP phosphorylation. Finally, when the preparations were exposed to an anoxia-reoxygenation protocol there was no difference in respiration compared to that of a heart sample from the same animal maintained under normoxia for the same time. When Complex I alone or Complex I and II were stimulated following one hour of anoxia there was no decline in oxygen flux observed. However, if Complex II was activated alone there was a significant decline in respiration. This decrease was however also observed in the mitochondria maintained in normoxia for one hour. In conclusion, Pacific hagfish cardiac mitochondria demonstrated a low rate of oxygen consumption, a loosely coupled electron transfer system, and a resistance to one hour of anoxia.

Remnant cholesterol is more positively related to diabetes, prediabetes, and insulin resistance than conventional lipid parameters and lipid ratios: A multicenter, large sample survey.

BACKGROUND: Not many large-sample investigations are available that compare the potency of the relationship of remnant cholesterol (RC) and other lipid parameters with diabetes and prediabetes. The goals of our study are to discover the relationship between RC and prediabetes, diabetes, and insulin resistance (IR) and to investigate RC, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C, which are the lipid parameters that are most positively related to diabetes, prediabetes, and IR. METHODS: This research enrolled 36 684 subjects from China's eight provinces. We employed multiple logistic regression analysis for testing the relationship between lipid parameters and diabetes, prediabetes, and IR. RESULTS: After adjusting for potential confounders, and comparing the results with other lipid parameters, the positive relationship between RC and diabetes (odds ratio [OR] 1.417, 95% confidence interval [CI]: 1.345-1.492), prediabetes (OR 1.555, 95% CI: 1.438-1.628), and IR (OR 1.488, 95% CI: 1.404-1.577) was highest. RC was still related to diabetes, prediabetes, and IR even when TG <2.3 mmol/L (diabetes: OR 1.256, 95% CI: 1.135-1.390; prediabetes: OR 1.503, 95% CI: 1.342-1.684; and IR: OR 1.278, 95% CI: 1.140-1.433), LDL-C <2.6 mmol/L (diabetes: OR 1.306, 95% CI: 1.203-1.418; prediabetes: OR 1.597, 95% CI: 1.418-1.798; and IR: OR 1.552, 95% CI: 1.416-1.701), or HDL-C ≥1 mmol/L (diabetes: OR 1.456, 95% CI: 1.366-1.550; prediabetes: OR 1.553, 95% CI: 1.421-1.697; and IR: OR 1.490, 95% CI: 1.389-1.598). CONCLUSION: RC is more positively related to diabetes, prediabetes, and IR than conventional lipids and lipid ratios in the general population, the relationships between RC and diabetes, prediabetes, and IR are stable, even if HDL-C, LDL-C, or TG are at appropriate levels.

Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.

BACKGROUND: Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other. METHODS: We employed non-synonymous-to-synonymous or dNdS ratios to evaluate the evolutionary dependency (ED) of gene pairs, assuming a mutation in one gene of a gene pair can affect the evolutionary fitness of mutations in its partner genes as mutation context. We employed PanCancer- and tumor type-specific mutational profiles to infer the ED of gene pairs and evaluated their biological relevance with respect to gene dependency and drug sensitivity. RESULTS: We propose that dNdS ratios of gene pairs and their derived cdNS (context-dependent dNdS) scores as measure of ED distinguishing gene pairs either as synergistic (SYN) or antagonistic (ANT). Mutation contexts can induce substantial changes in the evolutionary fitness of mutations in the paired genes, e.g., IDH1 and IDH2 mutation contexts lead to substantial increase and decrease of dNdS ratios of ATRX indels and IDH1 missense mutations corresponding to SYN and ANT relationship with positive and negative cdNS scores, respectively. The impact of gene silencing or knock-outs on cell viability (genetic dependencies) often depends on ED, suggesting that ED can guide the selection of candidates for synthetic lethality such as TCF7L2-KRAS mutations. Using cell line-based drug sensitivity data, the effects of targeted agents on cell lines are often associated with mutations of genes exhibiting ED with the target genes, informing drug sensitizing or resistant mutations for targeted inhibitors, e.g., PRSS1 and CTCF mutations as resistant mutations to EGFR and BRAF inhibitors for lung adenocarcinomas and melanomas, respectively. CONCLUSIONS: We propose that the ED of gene pairs evaluated by dNdS ratios can advance our understanding of the functional relationship of genes with potential biological and clinical implications.

Inflammatory Hematological Ratios in Adolescents with Mental Disorders: A Scoping Review.

BACKGOUND: Inflammatory hematological ratios (IHRs), such as neutrophil to lymphocyte, monocyte to lymphocyte, and platelet to lymphocyte ratios, are associated with mental disorders, symptoms severity, and the disease phase. Evidence from the studies in adult patients has been summarized in systematic reviews and meta-analyses. The results of the studies in adolescents remain poorly systematized. AIM: To summarize the findings from the studies that investigated the relationship of IHRs with mental disorders in adolescent patients. METHODS: This scoping review included studies of IHRs in patients aged 10-19 years with mental disorders (other than anorexia nervosa), published in English by December 31, 2023. The search for relevant papers was performed in MEDLINE. The studies were categorized into two groups: studies with external controls (healthy adolescents) and studies with internal controls (patients in different phases of mental disorder, with or without self-harm/suicidal behaviors). RESULTS: A total of 11 studies were included in the review (all cross-sectional ones). The results of these studies demonstrate that 1) adolescents with mental disorders (major depressive disorder, psychotic disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, substance use disorders) have higher IHR values than individuals of the same age without corresponding disorders (5 studies); 2) IHR values are positively correlated with the severity of psychopathological symptoms (1 study); 3) higher IHR values are associated with the phase of the mental disorder - manic episode in bipolar disorder (1 study) and exacerbation of psychosis in psychotic disorders (1 study); and 4) higher IHR values are associated with self-harm/suicidal behaviors - suicide attempts (1 study) and non-suicidal self-injury (1 study). CONCLUSION: IHRs are associated with mental disorders in adolescents, and higher IHR values are associated with a more severe/acute clinical presentation (severity of symptoms, mania, acute psychosis, self-harm/suicidal behaviors). Further studies of higher methodological quality are needed to evaluate the diagnostic and prognostic value of IHRs as biomarkers of mental disorders in adolescence.

Association between maternal lipid profiles and lipid ratios in early to middle pregnancy as well as their dynamic changes and gestational diabetes mellitus.

BACKGROUND: Unfavourable lipid and glucose levels may play a crucial role in the pathogenesis of gestational diabetes mellitus (GDM). However, there is a lack of prospective studies on the relationship between lipid profiles, lipid ratios and GDM during pregnancy. AIMS: To prospectively investigate the relationship between lipid profile and lipid ratios in early and mid-pregnancy and their pattern of change from early to mid-pregnancy and the risk of GDM. METHODS: This nested case-control study was based on maternal and child healthcare hospitals from Fujian Province, China. We included pregnant women who delivered in the hospital from January 2021 to June 2023. Lipid profiles (TC, TG, ApoA1, ApoB, HDL-c, LDL-c) and fasting glucose were measured before 14 weeks of gestation and between 20 and 28 weeks of gestation, and lipid ratios (triglyceride glucose index, TG/HDL-c and TC/HDL-c) was constructed. Logistic regression was used to assess the relationship between lipid profile, lipid ratios and GDM. RESULTS: Of 1586 pregnant women, 741 were diagnosed with GDM. After adjusting for potential confounders, TG, ApoA1, ApoB, LDL-c, triglyceride glucose index, TG/HDL-c, and TC/HDL-c in early pregnancy were positively associated with the risk of GDM (odds ratios [95% CI] for extreme interquartile comparisons were 2.040 (1.468-2.843), 1.506 (1.091-2.082), 1.529 (1.110-2.107), 1.504 (1.086-2.086), 1.952 (1.398-2.731), 2.127 (1.526-2.971), and 2.370 (1.700-3.312), all trend P < 0.05). HDL-c was negatively associated with the risk of GDM (0.639: 0.459-0.889, trend P all less than 0.05). Similarly, in mid-pregnancy, lower levels of HDL-c, higher levels of triglyceride glucose index, TG/HDL-c ratio, and TC/HDL-c ratio were associated with increased risk of GDM (all trends P < 0.05). Stably high levels (both ≥ median for early and mid-pregnancy) of triglyceride glucose index, TG/HDL-c and TC/HDL-c were associated with increased risk of GDM (OR [95% CI]: 2.369 (1.438-3.940), 1.588 (1.077-2.341), 1.921 (1.309-2.829), respectively). The opposite was true for HDL-c, where stable high levels were negatively associated with GDM risk (OR [95% CI]: 0.599 (0.405-0.883)). CONCLUSION: Increases in triglyceride glucose index, TG/HDL-c ratio, and TC/HDL-c ratio in early and mid-pregnancy, as well as their stable high levels from early to mid-pregnancy, are associated with a higher risk of GDM. In contrast, increased levels of HDL-c, both in early and mid-pregnancy, and their stable high levels from early to mid-pregnancy were associated with a lower risk of GDM. That highlighted their possible clinical relevance in identifying those at high risk of GDM.

Immune cell landscapes are associated with high-grade serous ovarian cancer survival.

High-grade serous ovarian cancer (HGSOC) is an aggressive disease known to develop resistance to chemotherapy. We investigated the prognostic significance of tumor cell states and potential mechanisms underlying chemotherapy resistance in HGSOC. Transcriptome deconvolution was performed to address cellular heterogeneity. Kaplan-Meier survival curves were plotted to illustrate the outcomes of patients with varying cellular abundances. The association between gene expression and chemotherapy response was tested. After adjusting for surgery status and grading, several cell states exhibited a significant correlation with patient survival. Cell states can organize into carcinoma ecotypes (CE). CE9 and CE10 were proinflammatory, characterized by higher immunoreactivity, and were associated with favorable survival outcomes. Ratios of cell states and ecotypes had better prognostic abilities than a single cell state or ecotype. A total of 1265 differentially expressed genes were identified between samples with high and low levels of C9 or CE10. These genes were partitioned into three co-expressed modules, which were associated with tumor cells and immune cells. Pogz was identified to be linked with immune cell genes and the chemotherapy response of paclitaxel. Collectively, the survival of HGSOC patients is correlated with specific cell states and ecotypes.

Enhancing the activation of T cells through anti-CD3/CD28 magnetic beads by adjusting the antibody ratio.

The utilization of anti-CD3/CD28 magnetic beads for T cell expansion in vitro has been investigated for adoptive cell transfer therapy. However, the impact of the CD3/CD28 antibody ratio on T cell differentiation and function remains incompletely elucidated. This study seeks to address this knowledge gap. To begin with, CD3 antibodies with a relatively low avidity for Jurkat cells (Kd = 13.55 nM) and CD28 antibodies with a relatively high avidity (Kd = 5.79 nM) were prepared. Afterwards, anti-CD3/CD28 antibodies with different mass ratios were attached to magnetic beads to examine the impacts of different antibody ratios on T cell capture, and proliferation. The research demonstrated that the most significant expansion of T cells was stimulated by the anti-CD3/CD28 magnetic beads with a mass ratio of 2:1 for CD3 antibodies and CD28 antibodies. Moreover, CD25 and PD1 expression of expanded T cells increased and then decreased, with lower CD25 and PD1 expression in the later stages of expansion indicating that T cells were not depleted. These T cells, which are massively expanded in vitro and have excellent expansion potential, can be infused back into the patient to treat tumor patients. This study shows that altering the ratio of anti-CD3/CD28 antibodies can control the strength of T cell stimulation, thereby leading to the improvement of T cell activation. This discovery can be utilized as a guide for the creation of other T cell stimulation approaches, which is beneficial for the further development of tumor immunotherapy technology.

Optimizing forage harvest and the nutritive value of Italian ryegrass-based mixed forage cropping under northwestern Himalayan conditions.

The scarcity of high-quality forage has a significant influence on the productivity and profitability of livestock. Addressing this concern, an investigation was undertaken to assess the effects of distinct Italian ryegrass genotypes, namely, Punjab ryegrass-1, Kashmir collection, and Makhan grass, in conjunction with varying seeding ratios of Italian ryegrass to Egyptian clover. The seeding ratios considered were 100:0 (Italian ryegrass to Egyptian clover), 75:25, 50:50, and 25:75. All possible combinations of Italian ryegrass and Egyptian clover with seeding ratios were set up in a randomized complete block design and replicated thrice. Co-cultivating Italian ryegrass and Egyptian clover at a 75:25 seeding ratio yields the best yield benefit, as determined by the land equivalent ratio. It is noteworthy that in this configuration, real yield loss is higher for Egyptian clover and for Italian ryegrass when the seeding ratio is 25:75. The higher competitiveness of Italian ryegrass in comparison to Egyptian clover is highlighted by the competitive ratio. Notably, the nutritive parameter, crude protein yield, was significantly higher in the Makhan grass-based 50:50 and 75:25 seeding ratio. Results of the study ascertained the compatibility of grass-legume co-cultivation with significantly higher quantity and quality forage harvested under mixed cropping systems whereas Makhan grass as the superior and dominant genotype in comparison to Kashmir collection. The outcomes of this study revealed that the 100:0 seeding ratio, coupled with the Makhan grass genotype, exhibited superior performance in terms of cumulative forage harvest, dry matter accumulation, net returns, and benefit-cost ratio.

Mapping the Grounds for Mortalities in Acute Myeloid Leukemia Through Registry Analyses: A Retrospective Cohort Study of Children, Adolescents, and Young Adults Patients.

Background: Our objective was to identify non-malignant factors that contribute to mortality in children, adolescents and young adults, aiming to improve patient follow-up and reduce mortality rates to achieve better survival outcomes. Methods: We analyzed 8,239 acute myeloid leukemia (AML) cases diagnosed between 2000 and 2019 in the USA. Using version 8.4.0.1 of the Surveillance, Epidemiology, and End Results (SEER)*Stat software, we calculated the standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) for each cause of death. Results: Out of the 3,165 deaths observed in the study population, the majority (2,245;70.9%) were attributed to AML itself, followed by non-AML cancers (573; 18.1%) and non-cancerous causes (347; 10.9%). Conclusions: Patients with AML are at a higher risk of developing other types of cancer and granulocyte deficiencies, which increases the risk of death from non-cancerous causes such as infections. Moreover, treatment for AML carries the risk of cardiac problems. AML is commoner in males than females.

Value of Vitamin D Metabolite Ratios in 3 Patients as Diagnostic Criteria to Assess Vitamin D Status.

Although clinical guidelines recommend measuring total plasma 25-hydroxyvitamin D (25[OH]D) to assess vitamin D (VitD) status, this index does not account for 3-fold inter-individual variation in VitD binding protein (VDBP) level. We present 3 individuals with total plasma 25(OH)D levels of 10.8 to 12.3 ng/mL (27-30.7 nmol/L). Because Endocrine Society guidelines define VitD deficiency as 25(OH)D ≤ 20 ng/mL (50 nmol/L), all 3 would be judged to be VitD deficient. VitD3 supplementation increased 25(OH)D to the range of 31.7 to 33.8 ng/mL (79.1-84.4 nmol/L). Patient #1 exhibited secondary hyperparathyroidism; VitD3 supplementation decreased parathyroid hormone (PTH) by 34% without a clinically significant change in PTH levels in the other 2 individuals. Thus, 25(OH)D level did not distinguish between the 1 patient who had secondary hyperparathyroidism and the 2 who did not. We therefore inquired whether VitD metabolite ratios (which are VDBP-independent) might distinguish among these 3 individuals. Of all the assessed ratios, the 1,25(OH)2D/24,25(OH)2D ratio was the most informative, which had a value of 102 pg/ng in the individual with secondary hyperparathyroidism but lower values (41 and 20 pg/ng) in the other 2 individuals. These cases illustrate the value of the 1,25(OH)2D/24,25(OH)2D ratio to provide clinically relevant information about VitD status.

Genetically predicted 1091 blood metabolites and 309 metabolite ratios in relation to risk of type 2 diabetes: a Mendelian randomization study.

Background: Metabolic dysregulation represents a defining characteristic of Type 2 diabetes (T2DM). Nevertheless, there remains an absence of substantial evidence establishing a direct causal link between circulating blood metabolites and the promotion or prevention of T2DM. In addressing this gap, we employed Mendelian randomization (MR) analysis to investigate the potential causal association between 1,091 blood metabolites, 309 metabolite ratios, and the occurrence of T2DM. Methods: Data encompassing single-nucleotide polymorphisms (SNPs) for 1,091 blood metabolites and 309 metabolite ratios were extracted from a Canadian Genome-wide association study (GWAS) involving 8,299 participants. To evaluate the causal link between these metabolites and Type 2 diabetes (T2DM), multiple methods including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode were employed. p-values underwent correction utilizing False Discovery Rates (FDR). Sensitivity analyses incorporated Cochran's Q test, MR-Egger intercept test, MR-PRESSO, Steiger test, leave-one-out analysis, and single SNP analysis. The causal effects were visualized via Circos plot, forest plot, and scatter plot. Furthermore, for noteworthy, an independent T2DM GWAS dataset (GCST006867) was utilized for replication analysis. Metabolic pathway analysis of closely correlated metabolites was conducted using MetaboAnalyst 5.0. Results: The IVW analysis method utilized in this study revealed 88 blood metabolites and 37 metabolite ratios demonstrating a significant causal relationship with T2DM (p < 0.05). Notably, strong causal associations with T2DM were observed for specific metabolites: 1-linoleoyl-GPE (18:2) (IVW: OR:0.930, 95% CI: 0.899-0.962, p = 2.16 × 10-5), 1,2-dilinoleoyl-GPE (18:2/18:2) (IVW: OR:0.942, 95% CI: 0.917-0.968, p = 1.64 × 10-5), Mannose (IVW: OR:1.133, 95% CI: 1.072-1.197, p = 1.02 × 10-5), X-21829 (IVW: OR:1.036, 95% CI: 1.036-1.122, p = 9.44 × 10-5), and Phosphate to mannose ratio (IVW: OR:0.870, 95% CI: 0.818-0.926, p = 1.29 × 10-5, FDR = 0.008). Additionally, metabolic pathway analysis highlighted six significant pathways associated with T2DM development: Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Glycerophospholipid metabolism, Alpha-Linolenic acid metabolism, Sphingolipid metabolism, and Alanine, aspartate, and glutamate metabolism. Conclusion: This study identifies both protective and risk-associated metabolites that play a causal role in the development of T2DM. By integrating genomics and metabolomics, it presents novel insights into the pathogenesis of T2DM. These findings hold potential implications for early screening, preventive measures, and treatment strategies for T2DM.

Compost amendment in urban gardens: elemental and isotopic analysis of soils and vegetable tissues.

Urban horticulture poses a sustainable form of food production, fosters community engagement and mitigates the impacts of climate change on cities. Yet, it can also be tied to health challenges related to soil contamination. This work builds on a previous study conducted on eleven urban gardens in the city of Vienna, Austria. Following the findings of elevated Pb levels in some soil and plant samples within that project, the present study investigates the elemental composition of soil and plants from two affected gardens 1 year after compost amendment. Inductively coupled plasma mass spectrometry (ICP-MS) analysis of skin, pulp and seeds of tomato fruits revealed minor variations in elemental composition which are unlikely to have an impact on food safety. In turn, a tendency of contaminant accumulation in root tips and leaves of radishes was found. Washing of lettuce led to a significant reduction in the contents of potentially toxic elements such as Be, Al, V, Ni, Ga and Tl, underscoring the significance of washing garden products before consumption. Furthermore, compost amendments led to promising results, with reduced Zn, Cd and Pb levels in radish bulbs. Pb isotope ratios in soil and spinach leaf samples taken in the previous study were assessed by multi-collector (MC-) ICP-MS to trace Pb uptake from soils into food. A direct linkage between the Pb isotopic signatures in soil and those in spinach leaves was observed, underscoring their effectiveness as tracers of Pb sources in the environment.

Survival-Related Genes on Chromosomes 6 and 17 in Medulloblastoma.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival-related genes (SRGs) using a gene expression dataset and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1) on chromosome 6, which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4ß, the MB subtype, with 93% deletion of 17p and 98% copy gain of 17q. GO enrichment analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provided a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosomes 6 and 17, warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

Evaluation of Plasma Atherogenic Index, Triglyceride-Glucose Index and Other Lipid Ratios as Predictive Biomarkers of Coronary Artery Disease in Different Age Groups.

(1) Background: Dyslipidaemia and insulin resistance are major risk factors for coronary artery disease (CAD). This study investigated the relationship between plasma atherogenic index (PA-I), triglyceride-glucose index (TGI) and other lipid ratios with the presence and prediction of CAD among different age categories. (2) Methods: The study included 223 participants diagnosed with CAD and those with normal coronary arteries (normal group) by coronary computed tomography angiography (CCTA). Participants were categorised by age and sex: premature CAD (PCAD) for men under 55 and women under 65, and older groups as elderly. (3) Results: PA-I, Lipid Combined Index, Castelli Risk Indices, and TGI were significantly higher in the PCAD group compared to the control group (p < 0.05). ROC analysis showed that a PA-I cut-off of 0.41 had a sensitivity of 62% and a specificity of 58% for predicting PCAD, while a TGI cut-off of 8.74 had a sensitivity of 68% and a specificity of 62%. In the elderly, no significant differences in these indices were found between the CAD and normal groups. (4) Conclusions: Traditional lipid profiles and non-traditional lipid indices such as PA-I and TGI show significant differences in predicting CAD in younger populations but not in older groups. TGI and PA-I may be promising biomarkers for the prediction of PAD, although further validation is needed.

Effects of a physical exercise programme on bodyweight, body condition score and chest, abdominal and thigh circumferences in dogs.

BACKGROUND: Research on the effects of physical exercise on canine body composition is limited. The aim of this study was to investigate the effects of a physical exercise programme on bodyweight, body condition score (BCS) and chest, abdominal and thigh circumferences in dogs. Twenty-one healthy dogs of different breeds exercised together with their owners during an eight-week programme consisting of jogging and strength exercises. Standardised measurements were performed in triplicates with a measuring tape on standing dogs. Chest circumference was measured at three anatomical locations, abdomen at two and thigh at one. Data on bodyweight, BCS (9-point scale) and circumferences were analysed with mixed model repeated measures analyses to evaluate changes after the programme and effects of target distance. RESULTS: Seven dog owners choose a target distance of 2 km and 14 owners choose 5-10 km. Mean BCS decreased (P = 0.007) after the programme (5.1 ± 0.9 vs. 4.7 ± 0.6) but there was no effect of target distance. Almost all chest and abdominal circumference measurements decreased (P ≤ 0.007) with the 2 km group driving the reduction in chest circumference and the 5-10 km group driving the reduction in abdominal circumference. In contrast, thigh circumference (28.8 ± 0.4 vs. 30.2 ± 0.4) increased (P = 0.007) while bodyweight was maintained. There were positive correlations between BCS and abdominal/chest ratios before and after the programme (Pearson correlation; R square ≤ 0.43, P ≤ 0.0012) but the mean ratio remained constant. CONCLUSIONS: Results indicated a redistribution between total body fat and muscle mass in body composition of normal weight to slightly overweight dogs after the physical exercise programme. The use of bodyweight alone was not a reliable evaluation method to complement the BCS assessment. However, repeated measurements of chest, abdominal and thigh circumference might aid in the assessment of body composition in dogs performing physical exercise. Further research should include a control group and objective evaluations of total body fat and lean mass, in order to investigate the effectiveness of physical exercise as a freestanding method for decreasing BCS and increasing muscle mass in overweight dogs.