Development Of An Elderly Female Torso Finite Element Model For Restraint System Research And Development Applications

Elderly females are found to be one of the most vulnerable segments of population during motor vehicle crashes and their population is increasing in the coming decades. Current design of restraint systems as well as other passive safety measures are designed based on anthropomorphic details of younger population. Developing another dummy representing elderly female population is a costly effort, while a finite element (FE) model of elderly female with similar anthropomorphic details and age- and gender-specific material properties can be a better alternative solution. The current research focuses on the development of a FE model of an elderly female torso, because a thorough search through literature has identified thorax as the most severely injured body part for elderly females due to rib fractures in motor vehicle induced trauma. Therefore, data from previously conducted rib bending experiments on 278 rib specimens taken from antero-lateral portion of 82 cadavers were analyzed to see the effect of age, gender, height, and weight on the rib bio-mechanical response parameters such as the maximum bending moment (MBM), maximum bending angle (Ɵmax), slope of moment-angle curve (SMT), and on average cortical thickness value. It was found that, in comparison to males, females had significantly lower values for the MBM (p = 0.000), SMT (p = 0.000), and average cortical-bone thickness (p = 0.001). Samples of ribs taken from elderly specimens failed at lower values of MBM than those from younger specimens, and had lower SMT, both in males and females (p \u3c 0.05). The generalized estimating equations were developed for each bio-mechanical response parameter in terms of dependent variables, namely the age, gender, height, and weight. Further, the material model parameters for elderly female rib specimen with constant cortical bone thickness were optimized, which in turn were used in developed whole body FE model. The cortical thickness variations in different sections (anterior, antero-lateral, lateral, posteo-lateral, and posterior) of whole rib were also assigned based on those reported in the literature. The model predicted peak responses as well as the fracture locations of the ribs were analyzed against whole rib bending tests with favorable result. Once the response of single whole rib was validated, further the response of elderly female whole rib cage was validated against data reported from frontal pendulum impacts at different speeds as well as data reported for belt loading. The validations results showed that the developed FE model can represent the overall behavior of elderly female during the type of loading as experienced in motor vehicle crashes

Clinico hematological profile of pancytopenia in pediatric patients: an institutional experience in North Himalayan region of India

Background: Pancytopenia is a common clinical pattern with an extensive differential diagnosis, but literature search shows only limited studies of pancytopenia in Pediatrics patients in Uttarakhand state of India. The present study was therefore conducted to study the spectrum of pancytopenia with bone marrow and haematological profile in Pediatrics patients in this north Himalayan state of India.Methods: Prospective observational study was conducted in the Department of Pediatrics in the teaching institute situated in Uttarakhand state of India over a period of 12 months. The study included all the patients of pancytopenia below 18 years of age who underwent bone marrow examination after written informed consent.Results: The study included total 50 pediatrics patients of pancytopenia with male to female ratio of 1.38:1. The mean age of patients was 10.58±4.94 with median age of 12 years. Mean hemoglobin was 5.31±2.09 g/dl, total leukocyte count was 2492.68±941.76/mm3, platelet count was 34724±26423/mm3, mean corpuscular volume was 90.95±16.65 fl, mean corpuscular hemoglobin was 30.11±6.07 pg, mean corpuscular hemoglobin concentration was 33.06±1.65% and reticulocyte count was 1.21±1.10%. Nutritional deficiency (28%) was the most common cause for pancytopenia followed by aplastic anemia (24%). Megaloblastic anemia was the commonest cause of nutritional deficiency anemia (71.42%) with pancytopenia.Conclusions: Pancytopenia is an important presentation in Pediatrics population with the most common cause being nutritional anemia and aplastic anemia. Megaloblastic anemia is the commonest cause of nutritional anemia with pancytopenia. The clinicians should be aware of spectrum of pancytopenia with clinical and haematological presentation in Pediatrics patients of this region so as to avoid unnecessary work ups and delay in treatment

Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis

AIM: To investigate gender-specific liver estrogen receptor (ER) expression in normal subjects and patients with hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC).METHODS: Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERa and ERB, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERa and ERB was further determined in nuclear and cytoplasmic tissue lysates along with the expression of inflammatory [activated NF-KB and IKB-kinase (IKK)] and oncogenic (cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERa and ERB was correlated with the expression of activated NF-KB, activated IKK and cyclin D1 by Spearman's correlation.RESULTS: Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERa than females (P < 0.05). We observed significantly higher mRNA expression of ERa in HCV-related HCC liver tissues as compared to normals (P < 0.05) and ERB in livers of HCV-related cirrhosis and HCV-related HCC subjects (P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERa in livers of HCV-related HCC patients and nuclear ERB in HCV-related cirrhosis patients as compared to normals (P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-KB and cyclin D1 in diseased livers (P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCV-infection may contribute to the progression of HCV-related cirrhosis to HCV-related HCC.CONCLUSION: Gender differences were observed in ERa expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence gender-related disparity in HCV-related pathogenesis.Peer reviewedBiochemistry and MicrobiologyHealth Care AdministrationStatistic

Cord bilirubin levels as a predictive marker for neonatal hyperbilirubinemia: A prospective study

Background: Hyperbilirubinemia is the most common medical problem in newborn infants. Early discharge is recommended but hospital readmission is a cause of concern among clinicians. This in turn carries a risk of delayed recognition of significant hyperbilirubinemia. Objective: A cross-sectional analytical study was done to evaluate the predictive value of cord bilirubin level for identifying term and near-term neonates for subsequent hyperbilirubinemia. Materials and Methods: Cord bilirubin levels at birth and subsequently serum bilirubin levels at 72 h were assessed in 100 neonates. The cutoff value was estimated beyond which there was significant hyperbilirubinemia. Results: The cutoff value of cord bilirubin &gt;2.02 mg/dl had sensitivity and specificity of 87.5-70.8%, respectively, with positive predictive value of 0.39 and negative predictive value of 0.965 for subsequent hyperbilirubinemia. Conclusion: The cutoff value of cord bilirubin level estimated is 2.02 mg/dl can be used to predict significant neonatal hyperbilirubinemia

Induced Opening of the Gastroesophageal Junction Occurs at a Lower Gastric Pressure in Gerd Patients and in Hiatal Hernia Subjects than in Normal Control Subjects

Purpose. To determine intragastric pressure threshold for inducing gastroesophageal junction (GEJ) opening in normal control subjects with and without hiatal hernia, and in patients with gastroesophageal reflux disease. Methods. This study was performed in 13 normal volunteers, 5 volunteers with hiatal hernia, and 3 patients with gastroesophageal reflux disease. During endoscopy a pressure transducer was used to measure baseline gastric pressures. The pressure in the stomach was measured while air was insufflated into the stomach until the gastroesophageal junction opened on endoscopic view. Results. There were two patterns of GEJ opening in normal volunteers. The mean opening pressure for Gastroesophageal junction in normal pattern-I, normal pattern-II, hiatal hernia, and Gastroesophageal reflux patients was 11.5, 12.6, 3.4, and 1.3 mmHg, respectively. Conclusions. GEJ opening is induced at a significantly lower pressure in subjects with hiatal hernia and in patients with gastroesophageal reflux disease than in normal volunteers

Population Pharmacokinetics of Olanzapine in Children

Aims The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed paediatric dosing scheme. Methods The PopPK of olanzapine was characterized using opportunistically collected plasma samples from children receiving olanzapine per standard of care for any indication. A nonlinear mixed effect modelling approach was employed for model development using the software NONMEM (v7.4). Simulations from the developed PopPK model were used to devise a paediatric dosing scheme that targeted comparable plasma exposures to adolescents and adults. Results Forty-five participants contributed 83 plasma samples towards the analysis. The median (range) postnatal age and body weight of participants were 3.8 years (0.2–19.2) and 14.1 kg (4.2–111.7), respectively. The analysis was restricted to pharmacokinetic (PK) samples collected following enteral administration (oral and feeding tube). A one-compartment model with linear elimination provided an appropriate fit to the data. The final model included the covariates body weight and postmenstrual age (PMA) on apparent olanzapine clearance (CL/F). Typical CL/F and apparent volume of distribution (scaled to 70 kg) were 16.8 L/h (21% RSE) and 663 L (13% RSE), respectively. Developed dosing schemes used weight-normalized doses for children ≤6 months postnatal age or \u3c15 kg and fixed doses for children ≥15 kg. Conclusion We developed a paediatric PopPK model for enterally-administered olanzapine. To our knowledge, this analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and PMA were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance

Gallbladder reporting and data system (GB-RADS) for risk stratification of gallbladder wall thickening on ultrasonography:an international expert consensus

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0–5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management. Graphical abstract: [Figure not available: see fulltext.]

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries