Tracking the Plasma C-Terminal Agrin Fragment as a Biomarker of Neuromuscular Decline in 18- to 87-Year-Old Men.

OBJECTIVES: Plasma C-terminal agrin-fragment-22 (CAF22), a breakdown product of neuromuscular junction, is a potential biomarker of muscle loss. However, its levels from adolescence to octogenarians are unknown. METHODS: We evaluated young (18-34 years, n = 203), middle-aged (35-59 years, n = 163), and old men (60-87 years, n = 143) for CAF22, handgrip strength (HGS), appendicular skeletal-mass index (ASMI), and gait speed. RESULTS: We found an age-associated increase in CAF22 from young (100.9 ± 29 pmol) to middle-aged (128.3 ± 38.7 pmol) and older men (171.5 ± 35.5 pmol) (all p<0.05). This was accompanied by a gradual reduction in HGS (37.7 ± 6.1 kg, 30.2 ± 5.2 kg, and 26.6 ± 4.7 kg, for young, middle-aged, and old men, respectively), ASMI (8.02 ± 1.02 kg/m2, 7.65 ± 0.92 kg/m2, 6.87 ± 0.93 kg/m2, for young, middle-aged, and old men, respectively), and gait speed (1.29 ± 0.24 m/s, 1.05 ± 0.16 m/s, and 0.81 ± 0.13 m/s, for young, middle-aged, and old men, respectively). After adjustment for age, we found negative regressions of CAF22 with HGS (- 0.0574, p < 0.001) and gait speed (- 0.0162, p < 0.001) in the cumulative cohort. The receiver operating characteristics analysis revealed significant efficacy of plasma CAF22 in diagnosing muscle weakness (HGS < 27 kg) (middle-aged men; AUC = 0.731, 95% CI = 0.629-0.831, p < 0.001, Older men; AUC = 0.816, 95% CI = 0.761-0.833, p < 0.001), and low gait speed (0.8 m/s) (middle-aged men; AUC = 0.737, 95% CI = 0.602-0.871, p < 0.001, older men; AUC = 0.829, 95% CI = 0.772-0.886, p < 0.001), and a modest efficacy in diagnosing sarcopenia (middle-aged men; AUC = 0.701, 95% CI = 0.536-0.865, p = 0.032, older men; AUC = 0.822, 95% CI = 0.759-0.884, p < 0.001) in middle-aged and older men. CONCLUSION: Altogether, CAF22 increases with advancing age and may be a reliable marker of muscle weakness and low gait speed.

Studying the Effect of the Host Genetic Background of Juvenile Polyposis Development Using Collaborative Cross and Smad4 Knock-Out Mouse Models.

Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder characterized by multiple juvenile polyps in the gastrointestinal tract, often associated with mutations in genes such as Smad4 and BMPR1A. This study explores the impact of Smad4 knock-out on the development of intestinal polyps using collaborative cross (CC) mice, a genetically diverse model. Our results reveal a significant increase in intestinal polyps in Smad4 knock-out mice across the entire population, emphasizing the broad influence of Smad4 on polyposis. Sex-specific analyses demonstrate higher polyp counts in knock-out males and females compared to their WT counterparts, with distinct correlation patterns. Line-specific effects highlight the nuanced response to Smad4 knock-out, underscoring the importance of genetic variability. Multimorbidity heat maps offer insights into complex relationships between polyp counts, locations, and sizes. Heritability analysis reveals a significant genetic basis for polyp counts and sizes, while machine learning models, including k-nearest neighbors and linear regression, identify key predictors, enhancing our understanding of juvenile polyposis genetics. Overall, this study provides new information on understanding the intricate genetic interplay in the context of Smad4 knock-out, offering valuable insights that could inform the identification of potential therapeutic targets for juvenile polyposis and related diseases.

Engineering Titanium-Hydroxyapatite Nanocomposite Hydrogels for Enhanced Antibacterial and Wound Healing Efficacy.

External factors often lead to predictable damage, such as chemical injuries, burns, incisions, and wounds. Bacterial resistance to antibiotics at wound sites underscores the importance of developing hydrogel composite systems with inorganic nanoparticles possessing antibacterial properties to treat infected wounds and expedite the skin regeneration process. In this study, a promising TiO2-HAp@PF-127@CBM inorganic and organic integrated hydrogel system was designed to address challenges associated with bacterial resistance and wound healing. The synthesized TiO2-hydroxyapatite (HAp) nanocomposites were coated with an FDA-approved PluronicF-127 polymer and combined with a carbomer hydrogel (CBM) to accomplish the final product. The synthesized nanoparticles exhibit enhanced biocompatibility against L929 and HUVECs and cell proliferation effects. To mitigate oxidative stress caused by TiO2-induced reactive oxygen species in dark environments for effective antibacterial effects, HAp promotes cell proliferation, expediting wound skin layer formation. CBM binds to inorganic nanoparticles, facilitating their gradual release and promoting wound healing. The reduced inflammation and enhanced tissue regeneration observed in the TiO2-HAp@PF-127@CBM group suggest a favorable environment for wound repair. These results align with prior findings highlighting the biocompatibility and wound-healing properties of titanium-HAp-based materials. The ability of the TiO2-HAp@PF-127@CBM hydrogel dressing to promote granulation tissue formation and facilitate epidermal regeneration underscores its potential for promoting antibacterial effects and wound healing applications.

Near-infrared-II responsive ovalbumin functionalized gold-genipin nanosystem cascading photo-immunotherapy of cancer.

Synergistic cancer therapies have attracted wide attention owing to their multi-mode tumor inhibition properties. Especially, photo-responsive photoimmunotherapy demonstrates an emerging cancer treatment paradigm that significantly improved treatment efficiency. Herein, near-infrared-II responsive ovalbumin functionalized Gold-Genipin nanosystem (Au-G-OVA NRs) was designed for immunotherapy and deep photothermal therapy of breast cancer. A facile synthesis method was employed to prepare the homogeneous Au nanorods (Au NRs) with good dispersion. The nanovaccine was developed further by the chemical cross-linking of Au-NRs, genipin and ovalbumin. The Au-G-OVA NRs outstanding aqueous solubility, and biocompatibility against normal and cancer cells. The designed NRs possessed enhanced localized surface plasmon resonance (LSPR) effect, which extended the NIR absorption in the second window, enabling promising photothermal properties. Moreover, genipin coating provided complimentary red fluorescent and prepared Au-G-OVA NRs showed significant intracellular encapsulation for efficient photoimmunotherapy outcomes. The designed nanosystem possessed deep photothermal therapy of breast cancer and 90% 4T1 cells were ablated by Au-G-OVA NRs (80µg ml-1concentration) after 1064 nm laser irradiation. In addition, Au-G-OVA NRs demonstrated outstanding vaccination phenomena by facilitating OVA delivery, antigen uptake, maturation of bone marrow dendritic cells, and cytokine IFN-γsecretion for tumor immunosurveillance. The aforementioned advantages permit the utilization of fluorescence imaging-guided photo-immunotherapy for cancers, demonstrating a straightforward approach for developing nanovaccines tailored to precise tumor treatment.

Breathing new life into tissue engineering: exploring cutting-edge vascularization strategies for skin substitutes.

Tissue-engineered skin substitutes (TESS) emerged as a new therapeutic option to improve skin transplantation. However, establishing an adequate and rapid vascularization in TESS is a critical factor for their clinical application and successful engraftment in patients. Therefore, several methods have been applied to improve the vascularization of skin substitutes including (i) modifying the structural and physicochemical properties of dermal scaffolds; (ii) activating biological scaffolds with growth factor-releasing systems or gene vectors; and (iii) developing prevascularized skin substitutes by loading scaffolds with capillary-forming cells. This review provides a detailed overview of the most recent and important developments in the vascularization strategies for skin substitutes. On the one hand, we present cell-based approaches using stem cells, microvascular fragments, adipose tissue derived stromal vascular fraction, endothelial cells derived from blood and skin as well as other pro-angiogenic stimulation methods. On the other hand, we discuss how distinct 3D bioprinting techniques and microfluidics, miRNA manipulation, cell sheet engineering and photosynthetic scaffolds like GelMA, can enhance skin vascularization for clinical applications. Finally, we summarize and discuss the challenges and prospects of the currently available vascularization techniques that may serve as a steppingstone to a mainstream application of skin tissue engineering.

Study of half-metallic ferromagnetism and transport characteristics of double perovskites Sr2AIrO6 (A = Y, Lu, Sc) for spintronic applications.

The precise manipulation of electromagnetic and thermoelectric characteristics in the miniaturization of electronic devices offers a promising foundation for practical applications in quantum computing. Double perovskites characterized by stability, non-toxicity, and spin polarization, have emerged as appealing candidates for spintronic applications. This study explores the theoretical elucidation of the influence of iridium's 5d electrons on the magnetic characteristics of Sr2AIrO6 (A = Y, Lu, Sc) with WIEN2k code. The determined formation energies confirm the thermodynamic stability while an analysis of band structure and the density of states (DOS) reveals a half-metallic ferromagnetic character. This characteristic is comprehensible through the analysis of exchange constants and exchange energies. The current analysis suggests that crystal field effects, a fundamental hybridization process and exchange energies contribute to the emergence of ferromagnetism due to electron-spin interactions. Finally, assessments of electrical and thermal conductivities, Seebeck coefficient, power factor, figure of merit and magnetic susceptibility are conducted to assess the potential of the investigated materials for the applications in thermoelectric devices.

Resistance Exercise Reduces Sarcopenia by Repairing Leaky Gut in Patients With Alzheimer's Disease.

PURPOSE: Sarcopenia or age-associated muscle loss is common in patients with Alzheimer's disease (AD). We have previously demonstrated the contribution of a leaky gut to sarcopenia in AD. Here, we asked whether resistant exercise (RE) reduces the sarcopenia phenotype by repairing intestinal leakage in patients with AD. METHOD: A prospective, single-center study of older adults, including healthy controls and patients with AD (n = 44-51/group), was conducted to measure plasma zonulin and claudin-3 (markers of intestinal leakage), handgrip strength (HGS), and short physical performance battery (SPPB) as a measure of functional capacity. Measurements in patients with AD were performed at baseline and after 12 weeks of RE. RESULTS: At baseline, patients with AD had higher plasma zonulin and claudin-3 and lower HGS, gait speed, and SPPB scores than controls. RE reduced plasma zonulin and claudin-3 levels and improved HGS, SPPB scores, and gait speed. Regression analysis revealed robust relationships between changes in plasma zonulin and claudin-3 with HGS. Plasma zonulin was also positively associated with SPPB scores. In addition, RE downregulated plasma markers of inflammation and oxidative stress. However, the prevalence of sarcopenia based on low HGS and muscle atrophy or low SPPB was not affected by RE. CONCLUSION: Taken together, disruption of the intestinal mucosal barrier may contribute to functional decline and sarcopenia in AD, which is incompletely recovered by RE. Circulating levels of zonulin and claudin-3 may be valuable in predicting sarcopenia and functional capacity in older adults with AD.

Impact of Postprocedural Graft Flow on Outcomes Following Chronic Total Occlusion Intervention in Postcoronary Artery Bypass Graft Patients: A Detailed Angiographic Analysis.

Chronic total occlusions (CTOs) are frequent in patients with previous coronary artery bypass graft (CABG) surgery. Percutaneous coronary intervention (PCI) is the usual revascularization strategy. Whether or not the presence of a graft on a CTO vessel and post-PCI graft patency impacts outcomes after CTO-PCI is unknown. We sought to evaluate the impact of post-PCI graft patency on the durability of CTO-PCI. In total, 259 patients with previous CABG who underwent CTO-PCI in 12 international centers in 2019 to 2023 were categorized into "grafted" and "ungrafted" groups based on the presence of graft on a CTO vessel. The grafted group was subdivided into "graft-occluded" and "graft-patent" groups, depending on graft patency. The primary end points were (1) technical success rate, (2) target vessel failure, and (3) CTO failure rates at 1 year. CTO failure was defined as target vessel revascularization and/or significant in-stent restenosis. A total of 199 patients (77%) were in the grafted group. Grafted CTOs showed higher complexity and lower technical success rates (70% vs 80%, p = 0.004) than nongrafted CTOs. Of the grafted CTOs, 140 (70%) were in the grafted-occluded group and 59 (30%) were in the grafted-patent group. The technical success was lower in the former group (65% vs 81%, p = 0.022). An occluded graft was an independent predictor of technical failure (odds ratio 2.04, 95% confidence interval 1.03 to 4.76, p = 0.049) and persistent post-PCI graft patency was a strong independent predictor of CTO failure at 1 year (hazard ratio 5.6, 95% confidence interval 1.2 to 27.5, log-rank p = 0.033). In conclusion, in patients with previous CABG who underwent CTO-PCI, post-PCI graft patency was a significant predictor of CTO failure.

Epidemiology and demographic patterns of cardiovascular diseases and neoplasms deaths in Western Europe: a 1990-2019 analysis.

OBJECTIVES: Cardiovascular diseases (CVDs) and neoplasms have been considered as public health concerns worldwide. This study aimed to estimate the epidemiological patterns of death burden on CVDs and neoplasms and its attributable risk factors in Western Europe from 1990 to 2019 to discuss the potential causes of the disparities. STUDY DESIGN AND METHODS: We collected data on CVDs and neoplasms deaths in 24 Western European countries from the Global Burden of Disease Study. We analyzed patterns by age, sex, country, and associated risk factors. The results include percentages of total deaths, age-standardized death rates per 100,000 population, and uncertainty intervals (UIs). Time trends were assessed using annual percent change. RESULTS: In 2019, CVDs and neoplasms accounted for 33.54% and 30.15% of Western Europe's total deaths, with age-standardized death rates of 128.05 (95% UI: 135.37, 113.02) and 137.51 (95% UI: 142.54, 128.01) per 100,000. Over 1990-2019, CVDs rates decreased by 54.97%, and neoplasms rates decreased by 19.54%. Top CVDs subtypes were ischemic heart disease and stroke; top cancers for neoplasms were lung and colorectal. Highest CVD death burdens were in Finland, Greece, Austria; neoplasm burdens in Monaco, San Marino, Andorra. The major risk factors were metabolic (CVDs) and behavioral (neoplasms). Gender differences revealed higher CVDs death burden in males, while neoplasms burden varied by risk factors and age groups. CONCLUSION: In 2019, CVDs and neoplasms posed significant health risks in Western Europe, with variations in death burdens and risk factors across genders, age groups, and countries. Future interventions should target vulnerable groups to lessen the impact of CVDs and neoplasms in the region.

Probiotics Supplements Improve the Sarcopenia-Related Quality of Life in Older Adults with Age-Related Muscle Decline.

A pathological increase in intestinal leak is implicated in age-associated muscle loss, termed sarcopenia, and reduced sarcopenia-related quality-of-life (SarQoL). However, the potential therapies remain elusive. We investigated the effects of probiotic supplementation on sarcopenia and SarQoL in geriatric older adults. We randomized sarcopenic men into placebo (age = 71.4 ± 3.9 years, n = 63) and probiotic (age = 73 ± 4.1 years, n = 60) groups for 16 weeks. The probiotic used was one capsule daily of Vivomix 112 billion for 16 weeks. We measured sarcopenia parameters of handgrip strength (HGS) and skeletal mass index (SMI), plasma zonulin (marker of the intestinal leak), and SarQoL using a targeted questionnaire. Probiotics improved the SarQoL scores for locomotion, functionality, and activities of daily living and prevented a decline in cumulative SarQoL observed in the placebo group (all p < 0.05). Probiotic supplementation also reduced plasma zonulin and marker of systemic bacterial load. These changes were accompanied by an increase in HGS and maintenance of gait speed in the probiotic group compared to the placebo group. Correlation analysis revealed significant associations of cumulative SarQoL scores with plasma zonulin and HGS in the probiotic group. Collectively, probiotics improved SarQoL and HGS by repairing pathological intestinal leak. Future studies may further dissect the relation between intestinal leak and SarQoL in older adults taking probiotics.

Metformin Improves Sarcopenia-Related Quality of Life in Geriatric Adults: A Randomized Controlled Trial.

OBJECTIVES: Metformin protects against age-related muscle decline, termed sarcopenia. However, the effects on sarcopenia quality-of-life (SarQoL) are unknown. We investigated the effects of metformin on SarQoL and associated mechanisms in older adults. METHOD: This double-blind randomized, placebo-controlled trial included geriatric adult men, divided into non-sarcopenic controls (age = 72.2 ± 4.3 years, n = 52) and two groups of patients with sarcopenia randomized into placebo (age at baseline = 74.4 ± 5.7 years, n = 54) and metformin (age at baseline = 71.2 ± 3.9 years, n = 47) groups. Patients in the metformin group received 1.7 grams twice daily for four months. We evaluated SarQoL, handgrip strength (HGS), plasma zonulin, c-reactive protein (CRP), and 8-isoprostanes. RESULTS: Patients with sarcopenia had lower HGS and SarQoL than controls (both p <0.05). Metformin improved the HGS and the SarQoL domains related to physical and mental health, locomotion, and leisure activities, as well as cumulative SarQoL scores (all p <0.05). Metformin also prevented the decline in the SarQoL domains for functionality and fear. Among plasma biomarkers, metformin reduced the levels of zonulin, CRP, 8-isoprostanes, and creatine kinase. We also found a significant correlation of plasma zonulin with cumulative SarQoL in patients with sarcopenia taking metformin, suggesting a role for intestinal repair in improving SarQoL. Finally, metformin did not affect body composition and gait speed. CONCLUSION: Overall, metformin improved HGS and SarQoL by repairing intestinal leakage. Our data have clinical relevance for improving the quality of life in older adults with sarcopenia.

Effect of asiatic acid supplementation in tris-extender on post-thaw functional competence, antioxidant enzyme activity and in vivo fertility of bull sperm.

Reactive oxygen species at supra-physiological levels trigger oxidative stress during cryopreservation, which can be neutralised by incorporating suitable antioxidants into the semen extender medium. This study was intended to explore the effect of asiatic acid (AA) as an antioxidant in semen extender on frozen-thawed sperm quality and in vivo fertility of bull sperm. Semen was collected from Holstein Friesian bulls for 10 consecutive weeks (total ejaculates = 60). Semen was cryopreserved with a Tris citric acid egg yolk-based extender supplemented with 0 (control), 20, 40, 60, and 100 µM AA. The supplementation of the extender with 40 and 60 µM AA improved (p < 0.05) post-thaw motility kinematics, plasma membrane integrity, acrosome integrity, sperm viability, and DNA integrity of bull sperm. Mitochondrial membrane potential was high (p < 0.05) with 60 µM of AA concentration in extender media. The catalase activity in seminal plasma was maintained (p < 0.05) when semen was added with 20, 40, and 60 µM of AA. The in vivo fertility was found to be significantly high with the semen extended with 60 µM AA. Conclusively, this study showed that AA supplementation in semen extender significantly improved sperm motility kinematics and cell integrity, conserved antioxidant enzyme activity, and improved in vivo fertility.

Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models.

BACKGROUND: Gold nanoparticles (GNPs) have been extensively recognized as an active candidate for a large variety of biomedical applications. However, the clinical conversion of specific types of GNPs has been hindered due to their potential liver toxicity. The origin of their hepatotoxicity and the underlying key factors are still ambiguous. Because the size, shape, and surfactant of GNPs all affect their properties and cytotoxicity. An effective and sensitive platform that can provide deep insights into the cause of GNPs' hepatotoxicity in vitro is therefore highly desired. METHODS: Here, hepatocyte organoid models (Hep-orgs) were constructed to evaluate the shape-dependent hepatotoxicity of GNPs. Two types of GNPs with different nanomorphology, gold nanospheres (GNSs) and spiny gold nanobranches (GNBs), were synthesized as the representative samples. Their shape-dependent effects on mice Hep-orgs' morphology, cellular cytoskeletal structure, mitochondrial structure, oxidative stress, and metabolism were carefully investigated. RESULTS: The results showed that GNBs with higher spikiness and tip curvature exhibited more significant cytotoxicity compared to the rounded GNSs. The spike structure of GNBs leads to a mitochondrial damage, oxidative stress, and metabolic disorder in Hep-orgs. Meanwhile, similar trends can be observed in HepG2 cells and mice models, demonstrating the reliability of the Hep-orgs. CONCLUSIONS: Hep-orgs can serve as an effective platform for exploring the interactions between GNPs and liver cells in a 3D perspective, filling the gap between 2D cell models and animal models. This work further revealed that organoids can be used as an indispensable tool to rapidly screen and explore the toxic mechanism of nanomaterials before considering their biomedical functionalities.

Facile synthesis of manganese-hafnium nanocomposites for multimodal MRI/CT imaging and in vitro photodynamic therapy of colon cancer.

Precise diagnosis of complex and soft tumors is challenging, which limits appropriate treatment options to achieve desired therapeutic outcomes. However, multifunctional nano-sized contrast enhancement agents based on nanoparticles improve the diagnosis accuracy of various diseases such as cancer. Herein, a facile manganese-hafnium nanocomposites (Mn3O4-HfO2 NCs) system was designed for bimodal magnetic resonance imaging (MRI)/computed tomography (CT) contrast enhancement with a complimentary function of photodynamic therapy. The solvothermal method was used to fabricate NCs, and the average size of Mn3O4 NPs and Mn3O4-HfO2 NCs was about 7 nm and 15 nm, respectively, as estimated by TEM. Dynamic light scattering results showed good dispersion and high negative (-33 eV) zeta potential, indicating excellent stability in an aqueous medium. Mn3O4-HfO2 NCs revealed negligible toxic effects on the NCTC clone 929 (L929) and mouse colon cancer cell line (CT26), demonstrating promising biocompatibility. The synthesized Mn3O4-HfO2 NCs exhibit significant enhancement in T1-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT), indicating the appropriateness for dual-modal MRI/CT molecular imaging probes. Moreover, ultra-small Mn3O4-HfO2 NCs show good relaxivities for MRI/CT. These nanoprobes Mn3O4-HfO2 NCs further possessed outstanding reactive oxygen species (ROS) generation ability under minute ultraviolet light (6 mW·cm-2) to ablate the colon cancer cells in vitro. Therefore, the designed multifunctional Mn3O4-HfO2 NCs were ideal candidates for cancer diagnosis and photodynamic therapy.

The Complexity of Skeletal Transverse Dimension: From Diagnosis, Management, and Treatment Strategies to the Application of Collaborative Cross (CC) Mouse Model.

This study investigates the significance of skeletal transverse dimension (STD) in orthodontic therapy and its impact on occlusal relationships. The primary goal is to enhance understanding and promote the integration of transverse skeletal diagnostics into routine orthodontic assessments. To achieve this aim, the study employs a comprehensive approach, utilizing model analysis, clinical assessments, radiographic measurements, and occlusograms. The initial step involves a meticulous assessment of deficiencies in the maxilla, mainly focusing on transverse dimension issues. Various successful diagnostic methods are employed to ascertain the type and presence of these deficiencies. Furthermore, the study compares surgically assisted maxillary expansion (SARME) and orthopedic maxillary expansion (OME) in addressing skeletal transverse issues. Stability assessments and efficacy analyses are conducted to provide valuable insights into the superiority of SARME over OME. The findings reveal that proper evaluation of STD is crucial in orthodontic diagnosis, as overlooking transverse dimension issues can lead to complications such as increased masticatory muscle activity, occlusal interferences, and an elevated risk of gingival recession. Surgically assisted maxillary expansion emerges as a more stable solution than orthopedic methods. In conclusion, incorporating skeletal transverse diagnostics into routine orthodontic assessments is imperative for achieving optimal occlusal relationships and minimizing negative consequences on dentition, periodontium, and joints. The study emphasizes the significance of accurate three-dimensional assessments and recommends the consideration of SARME over OME for addressing skeletal transverse deficiencies. Finally, the Collaborative Cross (CC) mouse model is also a novel mouse model for studying complex traits. Exploring the Collaborative Cross mouse model opens avenues for future research, promising further insights into transverse skeletal issues in orthodontics.

The 25-hydroxyvitamin D level in Kidney Transplant Recipients and Its Association With Renal Function and Other Cardio-Metabolic Risk Markers.

BACKGROUND: Vitamin D is the main hormone that plays a critical role in controlling mineral homeostasis. Transplant recipients frequently have altered levels of 25-hydroxyvitamin D (25[OH] D) and 1, 25-hydroxyvitamin (1, 25[OH] D). OBJECTIVES: To explore the status of vitamin D level in renal allograft recipients and its association with renal function and cardio-metabolic risk markers. METHODS: One hundred two adult kidney transplant recipients (KTRs) were included. Clinical history and information about transplantation and immunosuppression were recorded. Blood and urine samples were collected for relevant laboratory tests, including chronic kidney disease (CKD)-mineral and bone disorder markers (Ca, PO4, and 25[OH] D). RESULTS: The mean age was 35 ± 8 years, with a male/female ratio of 89/11%. The transplant duration was 34 ± 26 (4.5-112) months. All donors involved were living-related: fathers comprised 44%, wives 16%, sisters 13%, mothers 11%, and the others 16% (ie, brothers, sons, daughters, uncles, aunts). The immunosuppression regimen included prednisolone and tacrolimus in all, with mycophenolate mofetil in 96%. The estimated glomerular filtration rate showed CKD distribution from stage 1 to 5 in 6%, 29%, 44%, 15%, and 6%, respectively. Vitamin D level was lower in 22% (<20 ng/mL), insufficient (20-30 ng/mL) in 48%, and adequate (>30 ng/mL) in 30%. We compared different clinical and laboratory variables in 3 different vitamin D groups but found no difference in cardio-renal risk factors (P = Not Significant). Similarly, no correlation was seen between vitamin D levels and other clinical and metabolic factors. CONCLUSION: According to conventional cutoffs, the vitamin D (25[OH] D) level is inadequate in 70% of renal allograft recipients. The hormone level has no apparent association with renal function and major cardio-metabolic risk factors.

Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach.

BACKGROUND: Aspergillus fumigatus (Af) is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic background. The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus (Af) using an RNAseq approach in CC lines and hepatic gene expression. METHODS: We studied 31 male mice from 25 CC lines at 8 weeks old; the mice were infected with Af. Liver tissues were extracted from these mice 5 days post-infection, and next-generation RNA-sequencing (RNAseq) was performed. The GENE-E analysis platform was used to generate a clustered heat map matrix. RESULTS: Significant variation in body weight changes between CC lines was observed. Hepatic gene expression revealed 12 top prioritized candidate genes differentially expressed in resistant versus susceptible mice based on body weight changes. Interestingly, three candidate genes are located within genomic intervals of the previously mapped quantitative trait loci (QTL), including Gm16270 and Stox1 on chromosome 10 and Gm11033 on chromosome 8. CONCLUSIONS: Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af. As a next step, eQTL analysis will be performed for our RNA-Seq data. Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.