Prospective Research Comparing Different Trochanteric Fracture Fixation Techniques.

Aim Evaluation and comparison of various methods of trochanteric fracture fixation. Methods This study was conducted prospectively at the Orthopaedics Department of Dr. D Y Patil Medical College and Research Centre. The study spanned 18 months and involved 100 patients treated in the outpatient and the emergency department. Patients who fulfilled that specific criteria were selected for this study and the appropriate surgical intervention for each group was determined through radiological examination. Results Of the 100 patients, 55 (55%) were male and 45 (45%) females. Patients in our collection ranged from 20 to 90 years old. Proximal Femoral Nail (PFN), Dynamic Hip Screw (DHS ), and Proximal Femoral Locking Compression Plate (PFLCP ) groups averaged 56, 58, and 64 years old, respectively. The most common cause of intertrochanteric fracture was domestic falls (60%), followed by road traffic accidents (35%). The Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification rated 40 individuals (40%) as stable and 60 as unstable. Most patients in our study had unstable A3 fractures. PFN patients had 16 A3 fractures. In DHS, 32 patients suffered A3 fractures. Twelve PFLCP patients suffered A3 fractures. The smallest group had A1 fractures. Six PFN patients suffered A1 fractures. Two DHS patients had A1 fractures. Two PFLCP patients suffered A1 fractures. PFN group mean scores improved significantly after one and three months in this study. At six months, the PFN group had a significant mean score improvement. Conclusion PFN results ranged from satisfactory to excellent, offering numerous advantages over other methods such as DHS and PFLCP. The benefits of PFN include a shorter lever arm, fracture site compression, and enhanced rotational stability, which contribute to a lower chance of mechanical failure. Additionally, patients treated with PFN typically experience shorter hospital stays, earlier mobilization, less blood loss, shorter surgery times, faster rehabilitation, and quicker bone healing, making PFN a highly effective treatment option for certain fractures.

A Study Evaluating the Functional Outcomes of Mason Type III and IV Radial Head Fractures Treated With a Radial Head Prosthesis.

Objective This research aimed to assess the functional result of type III and IV radial head fractures that were treated using a radial head prosthesis. Methods A retrospective investigation was conducted on 70 patients with type III and IV radial head and neck fractures, as classified by Mason. The patients were hospitalized and received treatment at the Orthopaedics Department, where they had radial head prosthesis surgery for three years. Results Among the total of 70 cases, 42 (60%) cases were below the age of 40, while 28 (47%) cases were over 40 years. The average age was 36.4 years. The maximum age recorded was 54 years, while the lowest age recorded was 30 years. The female population outnumbered the male population. The majority of instances (42, 60%) were attributed to falls, while the remaining cases were caused by road traffic accidents (RTAs). Out of the total 70 instances, 52 cases (74.28%) exhibited right-side dominance, whereas 18 cases (25.72%) exhibited left-side dominance. Within our case study group, 56 (80%) cases fell under modified Mason's classification type Ill, totaling 56 instances. The remaining 20% of the cases, amounting to 11 cases, were classified as modified Mason's classification type IV. Among the 70 patients, 55 cases (78.58%) did not have any ligamentous damage, whereas seven (10%) cases had lateral ulnar collateral ligament (LUCL) injury and eight (11%) cases had medial collateral ligament (MCL) injury. The P value for flexion, extension, pronation, and supination was shown to be very significant. Out of the total, 47 (67%) instances had an MEPI score (Mayo Elbow Performance Index) of more than 90, indicating exceptional performance. In addition, 16 cases (22.85%) had an MEPI score ranging from 75 to 89, which is considered a good result. Lastly, seven cases (10%) had an MEPI score ranging from 60 to 74, indicating a fair result. Conclusion The use of a radial head prosthesis is considered a viable option for managing severe and irreparable fractures of the radial head. Effective outcomes hinge on meticulous preoperative planning, skilled intraoperative techniques, and intensive postoperative rehabilitation. These elements collectively contribute to achieving consistent and favorable results in patients undergoing this surgical intervention.

Diagnostic Utility of Cytomorphometric Evaluation of Exfoliated Oral Mucosal Cells in Type II Diabetes Mellitus: A Systematic Review and Meta-analysis.

Diabetes Mellitus (DM) is the sixth leading cause of mortality and morbidity in the world. Early diagnosis and periodic monitoring are mandatory to prevent complications. The custom of noninvasive exfoliative cytology diagnostic technique is the need of the hour in diabetes, where the invasive methods lose viability. The purpose of this meta-analysis is to analyze the cytomorphometric changes in the exfoliated cells of the oral mucosa, as an adjunct to the diagnosis of type II diabetes. A thorough search was made by using PubMed, Google Scholar, and Cochrane Library databases. Original research articles, that evaluated cytomorphometric parameters (nuclear area, cytoplasmic area, cytoplasmic nuclear ratio) in type II diabetes patients were included in this review. Risk of bias was analysed for each study using Joanna Briggs Institute and Review Manager was used for meta-analysis. All nine subgroups included for qualitative and quantitative data synthesis revealed that there was a significant increase in nuclear area and a decrease in cytoplasmic nuclear ratio in diabetic patients as compared to non-diabetics. Random-effects model also confirmed cytologically altered (nuclear area and cytoplasmic nuclear ratio) parameters to have a significantly increased risk of association with diabetes. Furthermore, these morphometry parameters were also associated with glycemic control and there was no gender disparity among them. Mounting evidence authenticate that cytomorphometric analysis of oral mucosal cells using exfoliative cytology might be aid as an adjunct non-invasive diagnostic tool for type II diabetes.

Unravelling the Significance of NLRP3 and IL-ß1 in Oral Squamous Cell Carcinoma and Potentially Malignant Oral Disorders: A Diagnostic and Prognostic Exploration.

BACKGROUND: Nucleotide-binding domain-like receptor protein 3 (NLRP3), an inflammasome, is reported to be dysregulated or aberrantly expressed in chronic inflammation, leading to a myriad of inflammatory disorders, autoimmune diseases, and cancer. This study aimed to explore the expression and role of NLRP3 protein and the secreted cytokine IL-ß1 in oral squamous cell carcinoma (OSCC) and potentially malignant oral disorders (PMOD). MATERIAL & METHODS: Tissue NLRP3 expression was quantified using sandwich ELISA in 30 cases each of OSCC, PMOD, and normal oral mucosa. Serum IL-ß1 level was also measured by ELISA to determine their correlation. In surgically treated OSCC cases, pathological parameters such as tumor size, depth of invasion (DOI), pTNM stage, and perineural & lymphovascular invasion were assessed and correlated with NLRP3 & IL-ß1 levels to investigate their roles in tumor progression, invasion, and metastasis. RESULTS: Tissue NLRP3 expression was markedly elevated in OSCC, with significant IL-ß1 levels observed in the serum of both OSCC and PMOD cases. Both markers showed a pronounced increase with the severity of dysplasia, indicating a strong association (p = 0.003%). The expression levels of tissue NLRP3 and serum IL-ß1 were positively correlated with DOI and tumor size. Furthermore, their elevated levels, alongside higher histological grades, indicate roles in the dedifferentiation and progression of tumor cells. CONCLUSION: The findings indicated that increased expression of NLRP3 and IL-ß1 in PMOD correlates with higher transformation rates, along with tumor progression and dedifferentiation in OSCC. Consequently, these markers hold promise as valuable targets for prognostic assessment, diagnostics, and therapeutic strategies in OSCC.

Radiological Evaluation of Lumbar Endplate Dimensions in the Indian Population and Their Correlation With Cage Placement/Length in Diverse Lumbar Fusion Techniques.

Background Lumbar fusion techniques are vital for treating various spinal conditions by promoting vertebral fusion to alleviate pain and restore stability. Given the anatomical uniqueness of the Indian skeletal structure, this study evaluates the radiological dimensions of lumbar endplates in the Indian population and their correlation with the placement and length of interbody cages used in various lumbar fusion techniques such as oblique lateral lumbar interbody fusion (OLIF), transforaminal lumbar interbody fusion (TLIF), and anterior lumbar interbody fusion (ALIF). This study aimed to conduct radiological measurements of lumbar endplates in the Indian population and correlate them with cage placement and length in lumbar fusion techniques. Methods This prospective study was conducted at the orthopaedic ward of a tertiary care center in Western Maharashtra, India. Healthy individuals (aged >18 years, either gender) selected with a 95% confidence level using Philip Core Integrity software (Amsterdam, Netherlands) were included in the study. We excluded those with a history of low back pain, previous lumbar spine surgeries, fractures, tuberculosis, tumors, deformities, degenerative diseases, or lesions affecting the lumbar spine. Quantitative measurements such as oblique and sagittal diameters, apophyseal ring widths, and interbody cage lengths were calculated using multiplanar reformatting with specific imaging parameters. Results A total of 150 individuals with an average age of 39.83 ± 14.17 years, ranging from 20 to 65 years. Among the study population, 68 were males and 82 were females. Among the male study population, oblique parameters such as Angle AOB and Mid-OD (oblique diameter) show considerable variability, with Angle AOB ranging from 51.43 ± 2.40 mm (L2 inferior) to 31.59 ± 4.25 mm (L5 inferior) and Mid-OD ranging from 41.59 ± 2.59 mm (L3 superior) to 34.38 ± 2.26 mm (S1 superior). Side-sagittal dimensions vary from 32.11 ± 2.50 mm (S1 superior) to 36.48 ±3.26 mm (L3 superior), emphasizing the need for tailored surgical planning. In contrast, females in the study population exhibit distinct anatomical profiles, with Angle AOB ranging from 52.15 ± 2.43 mm (L2 inferior) to 20.45 ± 5.45 mm (S1 superior) and Mid-OD from 33.48 ± 2.15 mm (L3 inferior) to 42.45 ± 2.59 mm (L3 superior). These findings underscore gender-specific anatomical differences crucial for individualized clinical evaluation and treatment strategies. Conclusion This study comprehensively analyzes oblique, side-sagittal, transverse, and midsagittal anatomic parameters across various vertebral levels in men and women, highlighting significant anatomical variations crucial for clinical assessments and surgical interventions.

Bilateral Humerus Midshaft Fracture Associated With Birth Trauma: A Case Report.

Bilateral humerus fractures as a result of birth trauma are a rare occurrence in neonatal care, necessitating special consideration due to their potential long-term implications. Birth-related injuries involving neonatal skeletal structures, especially fractures of the humerus, require special attention and a comprehensive approach to diagnosis and management. Here, we present the case of a newborn female child who experienced bilateral humerus fractures due to birth trauma. The subsequent management involved the application of splints to immobilize the affected arms, a standard practice in the treatment of fractures.

An enigmatic pathogenetic mechanism of hypoxia inducible factor - 1/2 alpha in the progression of fibrosis of oral submucous fibrosis and its malignant transformation: A systematic review and meta-analysis.

OBJECTIVE: Oral submucous fibrosis is a frequently reported potentially malignant disorder characterized by fibrosis and a malignant transformation rate of 7-30%. The role of hypoxia-inducible factor-1/2α in malignant transformation mechanisms of oral submucous fibrosis remains uncharted territory owing to a scarcity of studies. Thus the present systematic review and meta-analysis aimed to determine the role of hypoxia-inducible factor-1/2α in the progression of fibrosis of oral submucous fibrosis and its malignant transformation. MATERIAL AND METHODS: Using PubMed, Google Scholar, and Cochrane Library databases, full-text articles that investigated hypoxia-inducible factor-1/2α in oral submucous fibrosis were entailed for review. A modified Newcastle-Ottawa scale was employed to evaluate risk of bias in all articles and Review Manager was utilized for meta-analysis. RESULTS: Eighteen and eight qualified articles respectively were included for qualitative and quantitative data synthesis. Progressive upregulation of hypoxia-inducible factor-1/2α in oral submucous fibrosis is associated with fibrosis-induced carcinogenesis. A Random-effects model uncloaked that oral submucous fibrosis cases with significantly increased expression of hypoxia-inducible factor-1α had an increased associated risk of malignant transformation compared with controls (combined odds ratio 523.83, 95% confidence interval 125.74- 2182.28, p < 0.00001). CONCLUSION: The existing evidence substantiates the notion that hypoxia-inducible factor-1/2α, a fundamental pathogenetic mechanism of progression and malignant transformation of oral submucous fibrosis in the background of fibrosis.

Point biserial correlation symbiotic organism search nanoengineering based drug delivery for tumor diagnosis.

Nanoparticulate systems have the prospect of accounting for a new making of drug delivery systems. Nanotechnology is manifested to traverse the hurdle of both physical and biological sciences by implementing nanostructures indistinct fields of science, particularly in nano-based drug delivery. The low delivery efficiency of nanoparticles is a critical obstacle in the field of tumor diagnosis. Several nano-based drug delivery studies are focused on for tumor diagnosis. But, the nano-based drug delivery efficiency was not increased for tumor diagnosis. This work proposes a method called point biserial correlation symbiotic organism search nanoengineering-based drug delivery (PBC-SOSN). The objective and aim of the PBC-SOSN method is to achieve higher drug delivery efficiency and lesser drug delivery time for tumor diagnosis. The contribution of the PBC-SOSN is to optimized nanonengineering-based drug delivery with higher r drug delivery detection rate and smaller drug delivery error detection rate. Initially, raw data acquired from the nano-tumor dataset, and nano-drugs for glioblastoma dataset, overhead improved preprocessed samples are evolved using nano variational model decomposition-based preprocessing. After that, the preprocessed samples as input are subjected to variance analysis and point biserial correlation-based feature selection model. Finally, the preprocessed samples and features selected are subjected to symbiotic organism search nanoengineering (SOSN) to corroborate the objective. Based on these findings, point biserial correlation-based feature selection and a symbiotic organism search nanoengineering were tested for their modeling performance with a nano-tumor dataset and nano-drugs for glioblastoma dataset, finding the latter the better algorithm. Incorporated into the method is the potential to adjust the drug delivery detection rate and drug delivery error detection rate of the learned method based on selected features determined by nano variational model decomposition for efficient drug delivery.

Prognostic implications of CD-57 expression in oral squamous cell carcinoma cases.

Natural killer (NK) cells are one of the most important effector T -lymphocytes having antitumor effect. Only a few studies are present in the literature, correlating the expression of cluster of differentiation 57 (CD-57) in NK cells in oral squamous cell carcinoma (OSCC). To analyze the effect of the presence of NK cells in the stroma of OSCC and their effect on the tumor progression and prognosis. A retrospective study was performed over 122 OSCC patients who had undergone surgical treatment between 2014 and 16. Wax blocks were obtained and subjected to immunohistochemical (IHC) analysis for CD-57 expression. Patients were followed up for 3 years and 100 cases were finally included in the study and divided into three groups. The association between variable were studied through the Chi-square test, Kruskal-Wallis test, and Mann-Whitney U test. A total of 91% of cases showed positive staining for CD-57. Maximum positive expression (96.6%) was observed in the patients who were alive and without recurrence (Group-II) as compared to dead patients (Group-I) and in well-differentiated squamous cell carcinoma (WDSCC) cases (96.8%) than in poorly differentiated cases. Also, the mean CD-57 positive cells count was found to be highest in Group-II and WDSCC cases. A significant correlation was observed between CD-57 expression and patients' health status. As the expression of CD-57 increased in the tumor stroma of OSCC, the chances for the patient to be alive were increased; therefore, it may serve as a good prognostic marker.

An Analysis of Xpert Test for Diagnosing Maxillofacial Tuberculosis.

Background: Maxillofacial tuberculosis is a diagnostic challenge for surgeons. The aim of this study was to present a detailed analysis of Xpert test in diagnosing maxillofacial tuberculosis and to analyse the accuracy of Xpert test results for various tissues of maxillofacial region. Materials and Methods: In this cross-sectional study, patients were selected randomly from outpatient department. The patients who had clinical picture and differential diagnosis highly suggestive of maxillofacial tuberculosis were included. Patients were divided into three different groups depending upon the site of involvement. The samples collected from the patients were further subdivided depending upon the type of specimen. Patients were screened first by routine tests, and the negative cases were followed by Xpert test for tuberculosis. Results: A total of 54 patients were enrolled in the study, 13 patients were found to be positive for maxillofacial tuberculosis on routine screening tests for tuberculosis, and 41 tested negative on routine test and were evaluated further through Xpert test. Specimens from bone (n12), soft tissue and skin biopsy (n15) and aspirates from lymph nodes (n14) were obtained and tested. Twenty-one samples were found to be positive, and 20 were negative upon Xpert testing. There was a statistically significant difference seen between the test groups (p < 0.01) with higher frequency of negative results in routine test. The p value for various specimens containing pus, biopsies and aspirates was 0.045, 0.023 and 0.067, respectively. Conclusion: Xpert test is more accurate when compared to routine test for diagnosing maxillofacial tuberculosis. Although accuracy of Xpert test is better for pus and biopsy samples in the specimens from bone and soft tissue, it gives poor accuracy for aspirated cells. The aspirates from lymph nodes were more susceptible for false negative test.

Oncogenic signaling pathways in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common (∼90% cases) pancreatic neoplasm and one of the most lethal cancer among all malignances. PDAC harbor aberrant oncogenic signaling that may result from the multiple genetic and epigenetic alterations such as the mutation in driver genes (KRAS, CDKN2A, p53), genomic amplification of regulatory genes (MYC, IGF2BP2, ROIK3), deregulation of chromatin-modifying proteins (HDAC, WDR5) among others. A key event is the formation of Pancreatic Intraepithelial Neoplasia (PanIN) that often results from the activating mutation in KRAS. Mutated KRAS can direct a variety of signaling pathways and modulate downstream targets including MYC, which play an important role in cancer progression. In this review, we discuss recent literature shedding light on the origins of PDAC from the perspective of major oncogenic signaling pathways. We highlight how MYC directly and indirectly, with cooperation with KRAS, affect epigenetic reprogramming and metastasis. Additionally, we summarize the recent findings from single cell genomic approaches that highlight heterogeneity in PDAC and tumor microenvironment, and provide molecular avenues for PDAC treatment in the future.

Oncocytoma of the parotid gland: A rare benign tumour.

Oncocytomas are one of the infrequent neoplasms seen in the oral cavity accounting for less than 2% of all neoplasms in the oral cavity with less than 1% chance of malignant transformation. They affect the major salivary glands and have a female predilection. The cognisance of the unique clinical and histopathological features is very important to conclude a confirmatory diagnosis. This paper reviews a case of oncocytoma presented in our department and also elucidates the diagnostic criteria for the same.

Immunohistochemical expression of Ki-67 and Glypican-3 to distinguish aggressive from nonaggressive benign odontogenic tumors.

Background: The benign neoplasms are normally slow growing, indolent with no invasive potential. However, there exist a few locally aggressive benign odontogenic tumors that have a tendency to invade and deform the surrounding structures. The exact reason for the aggressiveness of these benign neoplasms remained an enigma. Their biology and clinical expression can often be destructive and ominous. An appropriate treatment protocol needs to be followed to combat the high recurrence rate and aggressiveness of these entities. Aggressive and noniaggressive epithelial odontogenic tumors were analyzed immunohistochemically with Ki-67 and glypican 3 (GPC3). Materials and Methods: Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, and 28 keratocystic odontogenic tumors) and nonaggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic itumors). Results: Statistical analysis using Pearson correlation showed Ki-67 to be a better marker for differentiating aggressive from nonaggressive odontogenic tumor as compared to GPC3 (P < 0.001, highly significant), whereas among aggressive tumors, GPC3 turned out to be more useful as compared to Ki-67 (P < 0.001, highly significant). Conclusion: The present study provides an insight into the different biological behavior of odontogenic tumors, which can thus be helpful in determining the therapy strategies for more aggressive odontogenic tumors.

Tibia Nailing Using Modular Stand: A Technical Note.

Interlocking nailing is a well-established procedure for managing unstable tibial shaft fractures. Closed reduction and internal fixation of the tibial shaft fractures require ease of intraoperative positioning, maneuvering, and biplane imaging. We describe the use of an innovative modular tibia-nailing stand, which greatly enhances the ergonomics of the tibia nailing procedure.

Symmetric and asymmetric receptor conformation continuum induced by a new insulin.

Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes and biochemical properties. Here, we report an active humanized cone snail venom insulin with an elongated A chain and a truncated B chain, and use cryo-electron microscopy (cryo-EM) and protein engineering to elucidate its interactions with the human insulin receptor (IR) ectodomain. We reveal how an extended A chain can compensate for deletion of B-chain residues, which are essential for activity of human insulin but also compromise therapeutic utility by delaying dissolution from the site of subcutaneous injection. This finding suggests approaches to developing improved therapeutic insulins. Curiously, the receptor displays a continuum of conformations from the symmetric state to a highly asymmetric low-abundance structure that displays coordination of a single humanized venom insulin using elements from both of the previously characterized site 1 and site 2 interactions.

Torso Kinematics in Human Rolling Do Not Change When Upper Extremity Motion Is Constrained.

Human rolling, as turning in bed, is a fundamental activity of daily living. A quantitative analysis of rolling could help identify the neuromusculoskeletal disorders that prohibit rolling and develop interventions for individuals who cannot roll. This study sought to determine whether crossing the arms over the chest would alter fundamental coordination patterns when rolling. Kinematic data were collected from 24 subjects as they rolled with and without their arms crossed over their chest. Crossing the arms decreased the mean peak angular velocities of the shoulders (p = .001) and pelvis (p = .013) and influenced the mean duration of the roll (p = .057). There were no fundamental differences in shoulder and pelvis coordination when rolling with the arms crossed over the chest, implying that the arms may not have a major role in rolling.

Chronic Oral Administration of Mineral Oil Compared With Corn Oil: Effects on Gut Permeability and Plasma Inflammatory and Lipid Biomarkers.

We investigated the effects of chronic oral administration of mineral oil, versus corn oil as control, on intestinal permeability, inflammatory markers, and plasma lipids in APOE*3-Leiden.CETP mice. Mice received mineral oil or corn oil 15 or 30 µL/mouse/day for 16 weeks (15 mice/group). Intestinal permeability was increased with mineral versus corn oil 30 µL/day, shown by increased mean plasma FITC-dextran concentrations 2 h post-administration (11 weeks: 1.5 versus 1.1 µg/ml, p = 0.02; 15 weeks: 1.7 versus 1.3 µg/ml, p = 0.08). Mean plasma lipopolysaccharide-binding protein levels were raised with mineral versus corn oil 30 µL/day (12 weeks: 5.8 versus 4.4 µg/ml, p = 0.03; 16 weeks: 5.8 versus 4.5 µg/ml, p = 0.09), indicating increased intestinal bacterial endotoxin absorption and potential pro-inflammatory effects. Plasma cholesterol and triglyceride concentrations were decreased with mineral oil, without affecting liver lipids among treated groups. Fecal neutral sterol measurements indicated increased fecal cholesterol excretion with mineral oil 30 µL/day (+16%; p = 0.04). Chronic oral administration of mineral oil in APOE*3-Leiden.CETP mice increased intestinal permeability, with potential pro-inflammatory effects, and decreased plasma cholesterol and triglyceride levels. Our findings may raise concerns about the use of mineral oil as a placebo in clinical studies.

Insulin action in the brain regulates both central and peripheral functions.

The brain has been traditionally thought to be insensitive to insulin, primarily because insulin does not stimulate glucose uptake/metabolism in the brain (as it does in classic insulin-sensitive tissues such as muscle, liver, and fat). However, over the past 20 years, research in this field has identified unique actions of insulin in the brain. There is accumulating evidence that insulin crosses into the brain and regulates central nervous system functions such as feeding, depression, and cognitive behavior. In addition, insulin acts in the brain to regulate systemic functions such as hepatic glucose production, lipolysis, lipogenesis, reproductive competence, and the sympathoadrenal response to hypoglycemia. Decrements in brain insulin action (or brain insulin resistance) can be observed in obesity, type 2 diabetes (T2DM), aging, and Alzheimer's disease (AD), indicating a possible link between metabolic and cognitive health. Here, we describe recent findings on the pleiotropic actions of insulin in the brain and highlight the precise sites, specific neuronal population, and roles for supportive astrocytic cells through which insulin acts in the brain. In addition, we also discuss how boosting brain insulin action could be a therapeutic option for people at an increased risk of developing metabolic and cognitive diseases such as AD and T2DM. Overall, this perspective article serves to highlight some of these key scientific findings, identify unresolved issues, and indicate future directions of research in this field that would serve to improve the lives of people with metabolic and cognitive dysfunctions.

Effects of mineral oil administration on the pharmacokinetics, metabolism and pharmacodynamics of atorvastatin and pravastatin in mice and dogs.

We investigated the effects of mineral oil on statin pharmacokinetics and inflammatory markers in animal models. A new synthesis strategy produced regioisomers that facilitated the characterization of the main metabolite (M1) of atorvastatin, a lipophilic statin, in C57BL/6NCrl mice. The chemical structure of M1 in mice was confirmed as ortho-hydroxy ß-oxidized atorvastatin. Atorvastatin and M1 pharmacokinetics and inflammatory markers were assessed in C57BL6/J mice given atorvastatin 5 mg/kg/day or 10 mg/kg/day, as a single dose or for 21 days, with or without 10 µL or 30 µL mineral oil. No consistent differences in plasma exposure of atorvastatin or M1 were observed in mice after single or repeat dosing of atorvastatin with or without mineral oil. However, mice administered atorvastatin 10 mg/kg with 30 µL mineral oil for 21 days had significantly increased plasma levels of serum amyloid A (mean 9.6 µg/mL vs 7.9 µg/mL without mineral oil; p < 0.01) and significantly increased proportions of C62Lhigh B cells (mean 18% vs 12% without mineral oil; p = 0.04). There were no statistically significant differences for other inflammatory markers assessed. In dogs, pharmacokinetics of atorvastatin, its two hydroxy metabolites and pravastatin (a hydrophilic statin) were evaluated after single administration of atorvastatin 10 mg plus pravastatin 40 mg with or without 2 g mineral oil. Pharmacokinetics of atorvastatin, hydroxylated atorvastatin metabolites or pravastatin were not significantly different after single dosing with or without mineral oil in dogs. Collectively, the results in mice and dogs indicate that mineral oil does not affect atorvastatin or pravastatin pharmacokinetics, but could cause low-grade inflammation with chronic oral administration, which warrants further investigation.

GeneCloudOmics: A Data Analytic Cloud Platform for High-Throughput Gene Expression Analysis.

Gene expression profiling techniques, such as DNA microarray and RNA-Sequencing, have provided significant impact on our understanding of biological systems. They contribute to almost all aspects of biomedical research, including studying developmental biology, host-parasite relationships, disease progression and drug effects. However, the high-throughput data generations present challenges for many wet experimentalists to analyze and take full advantage of such rich and complex data. Here we present GeneCloudOmics, an easy-to-use web server for high-throughput gene expression analysis that extends the functionality of our previous ABioTrans with several new tools, including protein datasets analysis, and a web interface. GeneCloudOmics allows both microarray and RNA-Seq data analysis with a comprehensive range of data analytics tools in one package that no other current standalone software or web-based tool can do. In total, GeneCloudOmics provides the user access to 23 different data analytical and bioinformatics tasks including reads normalization, scatter plots, linear/non-linear correlations, PCA, clustering (hierarchical, k-means, t-SNE, SOM), differential expression analyses, pathway enrichments, evolutionary analyses, pathological analyses, and protein-protein interaction (PPI) identifications. Furthermore, GeneCloudOmics allows the direct import of gene expression data from the NCBI Gene Expression Omnibus database. The user can perform all tasks rapidly through an intuitive graphical user interface that overcomes the hassle of coding, installing tools/packages/libraries and dealing with operating systems compatibility and version issues, complications that make data analysis tasks challenging for biologists. Thus, GeneCloudOmics is a one-stop open-source tool for gene expression data analysis and visualization. It is freely available at http://combio-sifbi.org/GeneCloudOmics.