Hepatocellular carcinoma (HCC) is primary hepatic malignancy with a high incidence of recurrence. The risk of recurrence directly correlates to patient’s overall prognosis. Management of advanced HCC ...involves a combination of surgical resection, locoregional therapy, and systemic treatment. Distant metastases are rare, and intraventricular cardiac metastases are even more infrequent. This brief review details an illustrative case of cardiac metastasis after curative treatment of primary HCC and then summarizes the literature on risk factors, treatment options, and patient prognosis in the setting of distant metastases from HCC. Prognosis of metastasis to the heart is generally poor, and available evidence emphasizes the importance of maintaining regular posttreatment screening for metastases in patients with HCC. Given the variable presentation and high risk of recurrence, it is critical to have individualized multimodality treatment plans.
Noncanonical splice-site mutations are an important cause of inherited diseases. Based on in vitro and stem-cell-based studies, some splice-site variants show a stronger splice defect than expected ...based on their predicted effects, suggesting that other sequence motifs influence the outcome. We investigated whether splice defects due to human-inherited-disease-associated variants in noncanonical splice-site sequences in
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could be rescued by strengthening the splice site on the other side of the exon. Noncanonical 5'- and 3'-splice-site variants were selected. Rescue variants were introduced based on an increase in predicted splice-site strength, and the effects of these variants were analyzed using in vitro splice assays in HEK293T cells. Exon skipping due to five variants in noncanonical splice sites of exons in
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could be partially or completely rescued by increasing the predicted strengths of the other splice site of the same exon. We named this mechanism "splicing interdependency", and it is likely based on exon recognition by splicing machinery. Awareness of this interdependency is of importance in the classification of noncanonical splice-site variants associated with disease and may open new opportunities for treatments.
Background. Diabetes mellitus is a metabolic disease which is seen increasing globally and is diagnosed and monitored on basis of invasive blood investigations. Salivary glands are affected in ...diabetes mellitus. The objective of this study was to assess ultrasonographic measurements of parotid glands and correlate with the glycosylated hemoglobin levels in type 2 diabetic mellitus and duration of type 2 diabetic mellitus and treatment regimens. Materials and Methods. This study was conducted on 50 subjects of type 2 diabetes mellitus and on 50 healthy controls. After HbA1C analysis of selected individuals, 100 individuals were grouped into group I (above 5.7) and group II (below 5.7). Ultrasonographic measurements (length (L), transverse dimension (TD), depth lateral to the mandible (DLM), and depth dorsal to the mandible (DDM)) of bilateral parotid glands were calculated. Statistical analysis was done using the chi-square test of significance and Spearman correlation coefficients. Results. On correlation with measurement of right (L, DLM, DDM) and left (TD, DLM, DDM) of parotid glands with duration of type 2 diabetes mellitus, we found a moderate positive relationship, whereas as for right (TD) and left (L), we found a low-positive relationship. Similarly, for right (L, TD, DLM, DDM) and left (TD, DDM) parotid glands with HbA1C, we found a low-positive relationship, whereas for left parotid gland (L, DLM) with HbA1C, we found a moderate positive relationship. The mean DLM of right and left parotids in the insulin group was found to be slightly more than that in the combined group which was statistically insignificant. Conclusion. Ultrasonographic measurements of parotid glands were found to be higher in study subjects as compared to control subjects, and they increased with increased HbA1C levels; also, there was no difference in treatment regimen. Ultrasonography could be a prospective diagnostic test for detection and monitoring of diabetes mellitus, and still further studies are required for this.
Background and aim
Since individuals in the early stages of liver cirrhosis are typically asymptomatic, the prevalence of liver cirrhosis may be underestimated. Liver cirrhosis has a significant ...morbidity and mortality rate, with 1.03 million deaths worldwide each year. For end-stage liver disease, liver transplantation is a potential therapeutic option. The goal of our research was to examine the current trend in liver transplants using data from a national database.
Methods
Using the International Classification of Diseases (ICD)-9 codes, we identified individuals who had a liver transplant during the index hospital admission in the Nationwide Inpatient Sample from 2007 to 2011. This national sample of patients is from the United States. We looked at the yearly trend in liver transplants and related outcomes, such as duration of hospitalization (DOH), hospital expenses, and mortality in the hospital. In order to find determinants of mortality, we used a multivariate analysis.
Results
There were 25,331 patients hospitalized (weighted for national estimate). Between 2007 and 2011, the number of transplants grew by 1.2%. The majority of transplant recipients were Caucasian (57%), with an average age of 54 years, had a private healthcare plan (53%), and had average earnings in the upper quartile by zip code (26%). Patients with a higher Charlson Comorbidity Index (79% had a score of four) were more likely to be admitted to a southern hospital (33%), an academic hospital (>99%), and a large capacity hospital (90%). Seventy percent of liver transplant recipients received cadaver donors. Hepatitis C was the most prevalent reason for transplant (30%), followed by hepatocellular carcinoma (HCC) (29%) and alcoholic liver disease (25%). In 2011, compared to 2007, there was an upward rise in fatality (from 3.8% to 5.1%), average hospital expenditures (from $335,504 to $498,369), and DOH (from 17.4 to 22.7 days). The cost of hospitalization was two billion dollars per year. The independent variables related to an increased mortality on multivariate analysis were African American race (OR: 2.0, 95%, CI: 1.2-3.2; p=0.005) and large capacity hospitals (OR: 2.5, 95% CI: 1.6-4.1; p=0.0002). Predictors linked to lower mortality included private healthcare coverage (vs. Medicare: OR: 0.7, 95%, CI: 0.51-0.97; p=0.03), academic hospital (OR: 0.6, 95% CI: 0.4-0.8; p=0.005), cadaver donor (OR: 0.6, 95% CI: 0.5-0.8; p=0.002), HCC (OR: 0.6, 95% CI: 0.4-0.9; p=0.01), and non-alcoholic steatohepatitis (NASH) cirrhosis (OR: 0.4, 95% CI: 0.2-0.9; p=0.02).
Conclusion
Our study found an increasing trend in worse outcomes (increased mortality, average hospital costs, and average DOH) after a liver transplant. Patients of the African American race and large capacity hospitals were associated with a higher risk of death, whereas private healthcare plans, academic hospitals, cadaver donors, HCC, and NASH cirrhosis were associated with a lower risk.
The first role of a civil engineer is to perform design and analyze the structure before it is built. The structure should provide a safe and green environment to live in and should take up less ...cost. Corbel is one of the complex structural members where the load applied is eccentric. Corbels can carry heavy loads under the bridges and must be designed for buckling and vibration analysis. The main focus of this study is to perform the reinforced cement concrete corbel using Midas NFX® and perform the static, buckling and vibration analysis. The results show whether the structure is safe in buckling and vibration. The buckling mode shapes and vibration mode shapes were presented. The topology optimization had been performed to identify the areas which carry loading with minimizing compliance as objective function. The optimal distribution of the material shows a strut and tie model in the design domain.
The ABCA4 gene is the most frequently mutated Mendelian retinopathy-associated gene. Biallelic variants lead to a variety of phenotypes, however, for thousands of cases the underlying variants remain ...unknown. Here, we aim to shed further light on the missing heritability of ABCA4-associated retinopathy by analyzing a large cohort of macular dystrophy probands. A total of 858 probands were collected from 26 centers, of whom 722 carried no or one pathogenic ABCA4 variant, while 136 cases carried two ABCA4 alleles, one of which was a frequent mild variant, suggesting that deep-intronic variants (DIVs) or other cis-modifiers might have been missed. After single molecule molecular inversion probes (smMIPs)-based sequencing of the complete 128-kb ABCA4 locus, the effect of putative splice variants was assessed in vitro by midigene splice assays in HEK293T cells. The breakpoints of copy number variants (CNVs) were determined by junction PCR and Sanger sequencing. ABCA4 sequence analysis solved 207 of 520 (39.8%) naive or unsolved cases and 70 of 202 (34.7%) monoallelic cases, while additional causal variants were identified in 54 of 136 (39.7%) probands carrying two variants. Seven novel DIVs and six novel non-canonical splice site variants were detected in a total of 35 alleles and characterized, including the c.6283-321C>G variant leading to a complex splicing defect. Additionally, four novel CNVs were identified and characterized in five alleles. These results confirm that smMIPs-based sequencing of the complete ABCA4 gene provides a cost-effective method to genetically solve retinopathy cases and that several rare structural and splice altering defects remain undiscovered in Stargardt disease cases.
ABCA4 sequence analysis in a heterogeneous cohort of ABCA4-associated retinopathy probands solved 277 of 722 (38.4%) cases, while additional variants were identified in 54 of 136 (39.7%) individuals known to already carry two variants. Additionally, complete ABCA4 locus sequencing lead to the identification of 13 novel splicing variants and four novel copy number variants.
Hereditary sensory and autonomic neuropathies (HSANs) are a group of disorders characterized by insensitivity to noxious stimuli and autonomic dysfunction, associated with pathological abnormalities ...of the peripheral nerves. Five types of HSAN have been reported in literature, out of which Type V known as congenital insensitivity to pain (CIP) is a rare autosomal recessive condition. Self-mutilation is an invariable feature of this disorder, involving the teeth and orofacial structures. This case report describes a case of a 6-year-old girl with CIP brought by her parents for prostheses to replace her self-extracted primary teeth.
Objectives: To assess the alveolar bone density by fractal dimension (FD) analysis in radiovisiograph of postmenopausal women of mandibular posterior region and to correlate FD values with t-scores ...of quantitative ultrasound of the calcaneus bone. Materials and Methods: This study, approved by the institutional review board, included 40 participants, aged 45-60 years divided into two groups. Twenty postmenopausal women with osteoporosis comprised group 1, and 20 postmenopausal women without osteoporosis comprised group 2 based on bone mineral density assessment of ultrasound of the calcaneus bone. Digital dental radiograph of mandibular first molar were obtained and used for assessing alveolar bone density by FD analysis and were correlated with t-scores of ultrasound of calcaneus bone. Results: The mean FD values were evaluated using SPSS 14 version software, and were found to be 1.738 and 1.867 for group 1 and group 2, respectively, which was statistically significant (P < 0.001). However, correlation between t-scores and FD values within the study group was not found to be statistically significant (P > 0.05). Conclusion: FD analysis using direct digital periapical radiographs is a novel method, which can be used for early diagnosis of osteoporosis in the alveolar bone.
Oral Submucous Fibrosis (OSF) is a precancerous condition of the oral mucosa. Existing treatments give only temporary symptomatic relief. Colchicine is an ancient drug with anti-fibrotic and ...anti-inflammatory properties. We planned to study the effects of colchicine in the management of oral submucous fibrosis.
Fifty OSF patients were divided randomly into two groups and treated for 12 weeks. Group 1-Patients were administered tablet colchicine orally, 0.5 mg twice daily and 0.5 ml intralesional injection Hyaluronidase 1,500 IU into each buccal mucosa once a week. Group 2-Patients were administered 0.5 ml intralesional injection Hyaluronidase 1,500 IU and 0.5 ml intralesional injection Hydrocortisone acetate 25 mg/ml in each buccal mucosa once a week alternatively. Student's t test and analysis of variance (ANOVA) were used to compare pre and post treatment results. P<0.05 was considered as significant.
Thirty-three percent in group 1 got relief from burning sensation in the second week. Inter group comparisons of increase in mouth opening and reduction in histological parameters indicated that group 1 patients responded better than group 2.
These encouraging results should prompt further clinical trials with colchicine alone on a larger sample size to broaden the therapeutic usefulness of the drug in the management of OSF.
The salivary fluid has an old history of study, but its physiological importance has only been recognized recently. In the past 50 years, the pace of salivary research has accelerated with the advent ...of new techniques that illuminated the biochemical and physicochemical properties of saliva. The interest in saliva increased, further, with the finding that saliva is filled with hundreds of components that might serve to detect systemic diseases and/or act as an evidence of exposure to various harmful substances as well as provide biomarkers of health and disease. The role of saliva in the diagnosis as well as monitoring of glycemic control has, also, been attracting attention of clinical researchers in recent times although results have been conflicting. To conclude, saliva is a whole, diverse fluid that serves various purposes discussed in detail in the literature. The recent introduction of molecular biology opens up, once again, new vistas and a new search of the role of salivary fluid as a potential diagnostic tool which has an added advantage of being noninvasive. The present review presents such insight into the possible use of salivary fluid as a potential diagnostic and prognostic tool for the search of numerous diseases as well as for monitoring the treatment outcomes and assesses prognosis in such varied states of derangements of metabolic functions.
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