Association of HOTAIR rs7958904 Polymorphism with Cervical Cancer Risk.

Cervical cancer (CC) has been the prominent cause of cancer-associated fatalities among women in developing countries. In terms of occurrence and mortality, it is ranked second in Bangladesh. Although different genetic polymorphisms linked with this cancer have been investigated over time, the association between the HOTAIR rs7958904 variant and cervical cancer is being reported for the first time in Bangladeshi women. RT-PCR-based TaqMan assay was employed to perform this case-control study on 200 cervical cancer patients and 148 healthy volunteers. Both cases and controls had average ages of 57.5 and 52.5 years, respectively. According to Hardy-Weinberg equilibrium, the rs7958904 allele of HOTAIR gene pretended no deviation for both cases and control groups. The genotyping results showed that rs7958904 has a significant correlation to the development of cervical cancer in different genetic association models, such as co-dominant 1 (CC vs. GG: OR = 1.67, p = 0.0435), co-dominant 2 (CC vs. GG: OR = 3.13, p = 0.0006), co-dominant 3 (CC vs. CG: OR = 1.88, p = 0.0384), dominant (CG + CC vs. GG: OR = 1.98, p = 0.004), recessive (CC vs. GG + CG: OR = 2.25, p = 0.005), and allele model (C vs. G: OR = 1.70, p = 0.0006). In conclusion, the HOTAIR rs7958904 variant has a substantial role in cervical cancer development in Bangladeshi women. Further functional studies with a larger population size are required to support our findings.

Deciphering KDM8 dysregulation and CpG methylation in hepatocellular carcinoma using multi-omics and machine learning.

Aim: This study investigates the altered expression and CpG methylation patterns of histone demethylase KDM8 in hepatocellular carcinoma (HCC), aiming to uncover insights and promising diagnostics biomarkers.Materials & methods: Leveraging TCGA-LIHC multi-omics data, we employed R/Bioconductor libraries and Cytoscape to analyze and construct a gene correlation network, and LASSO regression to develop an HCC-predictive model.Results: In HCC, KDM8 downregulation is correlated with CpGs hypermethylation. Differential gene correlation analysis unveiled a liver carcinoma-associated network marked by increased cell division and compromised liver-specific functions. The LASSO regression identified a highly accurate HCC prediction signature, prominently featuring CpG methylation at cg02871891.Conclusion: Our study uncovers CpG hypermethylation at cg02871891, possibly influencing KDM8 downregulation in HCC, suggesting these as promising biomarkers and targets.

Changes in gene function can play a role in causing cancer. In this study, we looked at how a specific gene called KDM8 behaves in liver cancer. By analyzing a large set of liver cancer samples, we investigated how gene interactions are different in this disease and if they can help predict liver cancer risk. Our results show that the KDM8 gene is less active, and its DNA gets chemically modified more often in liver cancer. We also found a group of genes and DNA changes, which are linked to the disease. Using this information, we identified 16 important markers and built a computer model that can accurately predict liver cancer. We found that DNA methylation at a specific spot called cg02871891 is especially important for predicting liver cancer. Overall, our study suggests that high levels of DNA methylation may lead to reduced KDM8 activity in liver cancer, which could be important for future research and better diagnostic tools.

In Silico Functional Characterization of a Hypothetical Protein From Pasteurella Multocida Reveals a Novel S-Adenosylmethionine-Dependent Methyltransferase Activity.

Genomes may now be sequenced in a matter of weeks, leading to an influx of "hypothetical" proteins (HP) whose activities remain a mystery in GenBank. The information included inside these genes has quickly grown in prominence. Thus, we selected to look closely at the structure and function of an HP (AFF25514.1; 246 residues) from Pasteurella multocida (PM) subsp. multocida str. HN06. Possible insights into bacterial adaptation to new environments and metabolic changes might be gained by studying the functions of this protein. The PM HN06 2293 gene encodes an alkaline cytoplasmic protein with a molecular weight of 28352.60 Da, an isoelectric point (pI) of 9.18, and an overall average hydropathicity of around -0.565. One of its functional domains, tRNA (adenine (37)-N6)-methyltransferase TrmO, is a S-adenosylmethionine (SAM)-dependent methyltransferase (MTase), suggesting that it belongs to the Class VIII SAM-dependent MTase family. The tertiary structures represented by HHpred and I-TASSER models were found to be flawless. We predicted the model's active site using the Computed Atlas of Surface Topography of Proteins (CASTp) and FTSite servers, and then displayed it in 3 dimensional (3D) using PyMOL and BIOVIA Discovery Studio. Based on molecular docking (MD) results, we know that HP interacts with SAM and S-adenosylhomocysteine (SAH), 2 crucial metabolites in the tRNA methylation process, with binding affinities of 7.4 and 7.5 kcal/mol, respectively. Molecular dynamic simulations (MDS) of the docked complex, which included only modest structural adjustments, corroborated the strong binding affinity of SAM and SAH to the HP. Evidence for HP's possible role as an SAM-dependent MTase was therefore given by the findings of Multiple sequence alignment (MSA), MD, and molecular dynamic modeling. These in silico data suggest that the investigated HP might be used as a useful adjunct in the investigation of Pasteurella infections and the development of drugs to treat zoonotic pasteurellosis.

Computational insights into the stereo-selectivity of catechins for the inhibition of the cancer therapeutic target EGFR kinase.

The epidermal growth factor receptor (EGFR) plays a crucial role in regulating cellular growth and survival, and its dysregulation is implicated in various cancers, making it a prime target for cancer therapy. Natural compounds known as catechins have garnered attention as promising anticancer agents. These compounds exert their anticancer effects through diverse mechanisms, primarily by inhibiting receptor tyrosine kinases (RTKs), a protein family that includes the notable member EGFR. Catechins, characterized by two chiral centers and stereoisomerism, demonstrate variations in chemical and physical properties due to differences in the spatial orientation of atoms. Although previous studies have explored the membrane fluidity effects and transport across cellular membranes, the stereo-selectivity of catechins concerning EGFR kinase inhibition remains unexplored. In this study, we investigated the stereo-selectivity of catechins in inhibiting EGFR kinase, both in its wild-type and in the prevalent L858R mutant. Computational analyses indicated that all stereoisomers, including the extensively studied catechin (-)-EGCG, effectively bound within the ATP-binding site, potentially inhibiting EGFR kinase activity. Notably, gallated catechins emerged as superior EGFR inhibitors to their non-gallated counterparts, revealing intriguing binding trends. The top four stereoisomers exhibiting high dock scores and binding energies with wild-type EGFR comprise (-)-CG (-)-GCG (+)-CG, and (-)-EGCG. To assess dynamic behavior and stability, molecular dynamics simulations over 100 ns were conducted for the top-ranked catechin (-)-CG and the widely investigated catechin (-)-EGCG with EGFR kinase. This study enhances our understanding of how the stereoisomeric nature of a drug influences inhibitory potential, providing insights that could guide the selection of specific stereoisomers for improved efficacy inexisting drugs.

A Systems Biology and LASSO-Based Approach to Decipher the Transcriptome-Interactome Signature for Predicting Non-Small Cell Lung Cancer.

The lack of precise molecular signatures limits the early diagnosis of non-small cell lung cancer (NSCLC). The present study used gene expression data and interaction networks to develop a highly accurate model with the least absolute shrinkage and selection operator (LASSO) for predicting NSCLC. The differentially expressed genes (DEGs) were identified in NSCLC compared with normal tissues using TCGA and GTEx data. A biological network was constructed using DEGs, and the top 20 upregulated and 20 downregulated hub genes were identified. These hub genes were used to identify signature genes with penalized logistic regression using the LASSO to predict NSCLC. Our model's development involved the following steps: (i) the dataset was divided into 80% for training (TR) and 20% for testing (TD1); (ii) a LASSO logistic regression analysis was performed on the TR with 10-fold cross-validation and identified a combination of 17 genes as NSCLC predictors, which were used further for development of the LASSO model. The model's performance was assessed on the TD1 dataset and achieved an accuracy and an area under the curve of the receiver operating characteristics (AUC-ROC) of 0.986 and 0.998, respectively. Furthermore, the performance of the LASSO model was evaluated using three independent NSCLC test datasets (GSE18842, GSE27262, GSE19804) and achieved high accuracy, with an AUC-ROC of >0.99, >0.99, and 0.95, respectively. Based on this study, a web application called NSCLCpred was developed to predict NSCLC.

Molecular approaches in cancer.

Cancer remains the second leading cause of death worldwide and newly diagnosed cases have increased at an alarming rate. One in every four people has a lifetime risk of being afflicted with cancer. Early diagnosis, which is essential in reducing morbidity and mortality, requires the development of highly sensitive and specific techniques to identify and monitor molecular changes for cancer-specific genetic and epigenetic markers. Among these, fluorescent in situ hybridization (FISH), Polymerase Chain Reaction (PCR), DNA microarray and NanoString technologies are notable. Recent advances in the development of efficient and cost-effective next-generation sequencing (NGS) has enabled whole genome, exome and transcriptome analysis. This review focuses on the features and applications of important molecular techniques to detect various genetic mutations thus enabling improved diagnosis, treatment and outcome.

Aspirin attenuates the expression of adhesion molecules, risk of obesity, and adipose tissue inflammation in high-fat diet-induced obese mice.

The prevalence of obesity is increasing at an alarming rate and keeps on being one of the significant challenges of this century. Obesity promotes adipose tissue hypertrophy and causes the release of different pro-inflammatory cytokines, playing a significant role in the pathophysiology of metabolic syndrome. Aspirin is known as a potent anti-inflammatory drug, but its role in adipogenesis, adipocyte-specific inflammation, and metabolic syndrome is not well characterized. Thus, in this experiment, we aimed to determine the effect of low-dose aspirin on obesity, obesity-induced inflammation, and metabolic syndrome. High-fat diet-induced obese female mice (Swiss Albino) were used in our study. Mice were fed on a normal diet, a high-fat diet, and a low dose of aspirin (LDA) in the presence of a high-fat diet for 11 weeks. Body weight, lipid profile, adipose tissue size, and inflammatory status were analyzed after that period. The ∆∆CT method was used to calculate the relative mRNA expression of target genes. Treatment with a low dose of aspirin resulted in a significant reduction of body weight, visceral fat mass and serum total cholesterols, serum and adipose tissue triglycerides, and blood glucose levels in high-fat diet-induced obese mice compared to the untreated obese group. Consistent with these biochemical results, a significant reduction in mRNA expression of different genes like PPARγ, GLUT4, IL-6, TNFα, MCP-1, ICAM-I, and VCAM-I associated with adipogenesis and inflammation were noticed. Overall, current study findings indicate that low-dose aspirin reduces obesity, hyperlipidemia, adipocyte-specific inflammation, and metabolic syndrome in high-fat diet-induced obese mice.

The Histone H3K27me3 Demethylases KDM6A/B Resist Anoikis and Transcriptionally Regulate Stemness-Related Genes.

Epithelial cancer cells that lose attachment from the extracellular matrix (ECM) to seed in a distant organ often undergo anoikis's specialized form of apoptosis. Recently, KDM3A (H3K9 demethylase) has been identified as a critical effector of anoikis in cancer cells. However, whether other histone demethylases are involved in promoting or resisting anoikis remains elusive. We screened the major histone demethylases and found that both H3K27 histone demethylases, namely, KDM6A/B were highly expressed during ECM detachment. Inhibition of the KDM6A/B activity by using a specific inhibitor results in reduced sphere formation capacity and increased apoptosis. Knockout of KDM6B leads to the loss of stem cell properties in solitary cells. Furthermore, we found that KDM6B maintains stemness by transcriptionally regulating the expression of stemness genes SOX2, SOX9, and CD44 in detached cells. KDM6B occupies the promoter region of both SOX2 and CD44 to regulate their expression epigenetically. We also noticed an increased occupancy of the HIF1α promoter by KDM6B, suggesting its regulatory role in maintaining hypoxia in detached cancer cells. This observation was further strengthened as we found a significant positive association in the expression of both KDM6B and HIF1α in various cancer types. Overall, our results reveal a novel transcriptional program that regulates resistance against anoikis and maintains stemness-like properties.

A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm.

BACKGROUND: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the coronavirus disease of 2019 (COVID-19) that killed more than 3.5 million people till now. The cytokine storm induced in severe COVID-19 patients causes hyper-inflammation, is the primary reason for respiratory and multi-organ failure and fatality. This work uses a rational computational strategy to identify the existing drug molecules to target host pathways to reduce the cytokine storm. RESULTS: We used a "host response signature network" consist of 36 genes induced by SARS-CoV-2 infection and associated with cytokine storm. In order to attenuate the cytokine storm, potential drug molecules were searched against "host response signature network". Our study identified that drug molecule andrographolide, naturally present in a medicinal plant Andrographis paniculata, has the potential to bind with crucial proteins to block the TNF-induced NFkB1 signaling pathway responsible for cytokine storm in COVID-19 patients. The molecular docking method showed the binding of andrographolide with TNF and covalent binding with NFkB1 proteins of the TNF signaling pathway. CONCLUSION: We used a rational computational approach to repurpose existing drugs targeting host immunomodulating pathways. Our study suggests that andrographolide could bind with TNF and NFkB1 proteins, block TNF-induced cytokine storm in COVID-19 patients, and warrant further experimental validation.

pssRNAit: A Web Server for Designing Effective and Specific Plant siRNAs with Genome-Wide Off-Target Assessment.

We report an advanced web server, the plant-specific small noncoding RNA interference tool pssRNAit, which can be used to design a pool of small interfering RNAs (siRNAs) for highly effective, specific, and nontoxic gene silencing in plants. In developing this tool, we integrated the transcript dataset of plants, several rules governing gene silencing, and a series of computational models of the biological mechanism of the RNA interference (RNAi) pathway. The designed pool of siRNAs can be used to construct a long double-strand RNA and expressed through virus-induced gene silencing (VIGS) or synthetic transacting siRNA vectors for gene silencing. We demonstrated the performance of pssRNAit by designing and expressing the VIGS constructs to silence Phytoene desaturase (PDS) or a ribosomal protein-encoding gene, RPL10 (QM), in Nicotiana benthamiana We analyzed the expression levels of predicted intended-target and off-target genes using reverse transcription quantitative PCR. We further conducted an RNA-sequencing-based transcriptome analysis to assess genome-wide off-target gene silencing triggered by the fragments that were designed by pssRNAit, targeting different homologous regions of the PDS gene. Our analyses confirmed the high accuracy of siRNA constructs designed using pssRNAit The pssRNAit server, freely available at https://plantgrn.noble.org/pssRNAit/, supports the design of highly effective and specific RNAi, VIGS, or synthetic transacting siRNA constructs for high-throughput functional genomics and trait improvement in >160 plant species.

Investigating the pathogenic SNPs in BLM helicase and their biological consequences by computational approach.

The BLM helicase protein plays a vital role in DNA replication and the maintenance of genomic integrity. Variation in the BLM helicase gene resulted in defects in the DNA repair mechanism and was reported to be associated with Bloom syndrome (BS) and cancer. Despite extensive investigation of helicase proteins in humans, no attempt has previously been made to comprehensively analyse the single nucleotide polymorphism (SNPs) of the BLM gene. In this study, a comprehensive analysis of SNPs on the BLM gene was performed to identify, characterize and validate the pathogenic SNPs using computational approaches. We obtained SNP data from the dbSNP database version 150 and mapped these data to the genomic coordinates of the "NM_000057.3" transcript expressing BLM helicase (P54132). There were 607 SNPs mapped to missense, 29 SNPs mapped to nonsense, and 19 SNPs mapped to 3'-UTR regions. Initially, we used many consensus tools of SIFT, PROVEAN, Condel, and PolyPhen-2, which together increased the accuracy of prediction and identified 18 highly pathogenic non-synonymous SNPs (nsSNPs) out of 607 SNPs. Subsequently, these 18 high-confidence pathogenic nsSNPs were analysed for BLM protein stability, structure-function relationships and disease associations using various bioinformatics tools. These 18 mutants of the BLM protein along with the native protein were further investigated using molecular dynamics simulations to examine the structural consequences of the mutations, which might reveal their malfunction and contribution to disease. In addition, 28 SNPs were predicted as "stop gained" nonsense SNPs and one SNP was predicted as "start lost". Two SNPs in the 3'UTR were found to abolish miRNA binding and thus may enhance the expression of BLM. Interestingly, we found that BLM mRNA overexpression is associated with different types of cancers. Further investigation showed that the dysregulation of BLM is associated with poor overall survival (OS) for lung and gastric cancer patients and hence led to the conclusion that BLM has the potential to be used as an important prognostic marker for the detection of lung and gastric cancer.

Integrated Network Analysis Reveals FOXM1 and MYBL2 as Key Regulators of Cell Proliferation in Non-small Cell Lung Cancer.

Background: Loss of control on cell division is an important factor for the development of non-small cell lung cancer (NSCLC), however, its molecular mechanism and gene regulatory network are not clearly understood. This study utilized the systems bioinformatics approach to reveal the "driver-network" involve in tumorigenic processes in NSCLC. Methods: A meta-analysis of gene expression data of NSCLC was integrated with protein-protein interaction (PPI) data to construct an NSCLC network. MCODE and iRegulone were used to identify the local clusters and its upstream transcription regulators involve in NSCLC. Pair-wise gene expression correlation was performed using GEPIA. The survival analysis was performed by the Kaplan-Meier plot. Results: This study identified a local "driver-network" with highest MCODE score having 26 up-regulated genes involved in the process of cell proliferation in NSCLC. Interestingly, the "driver-network" is under the regulation of TFs FOXM1 and MYBL2 as well as miRNAs. Furthermore, the overexpression of member genes in "driver-network" and the TFs are associated with poor overall survival (OS) in NSCLC patients. Conclusion: This study identified a local "driver-network" and its upstream regulators responsible for the cell proliferation in NSCLC, which could be promising biomarkers and therapeutic targets for NSCLC treatment.

A molecular bridge: connecting type 2 diabetes and Alzheimer's disease.

Type 2 diabetes (T2D) and Alzheimer's disease (AD) are complex diseases commonly associated with aging. Accumulating evidence indicates a connection between these two diseases at the molecular level. Much of what we currently know about T2D and AD is derived from in vivo and in vitro studies. However, further research and characterization of molecules is necessary to establish a strong connection between T2D and AD. In silico studies play a major role in finding non-evident patterns of gene expression and gene network connectivity. In this review, we give a brief introduction to T2D and AD and then describe the risk factors and molecules that are commonly associated with these diseases. Finally, we discuss the future directions and applications of bioinformatics that can provide greater insight into the relationship between these two diseases. Analysis and integration of high-throughput data on genomics, transcriptomics, proteomics and metabolomics from normal and disease tissues would be very useful to improve our understanding of the mechanism behind disease initiation and the connection between these two diseases. We encourage researchers to use bioinformatics approaches to identify genes and their regulatory pathways that are commonly affected in T2D and AD, as these genes and pathways could be potential biomarkers and targets for disease treatment.

HIVsirDB: a database of HIV inhibiting siRNAs.

BACKGROUND: Human immunodeficiency virus (HIV) is responsible for millions of deaths every year. The current treatment involves the use of multiple antiretroviral agents that may harm patients due to their toxic nature. RNA interference (RNAi) is a potent candidate for the future treatment of HIV, uses short interfering RNA (siRNA/shRNA) for silencing HIV genes. In this study, attempts have been made to create a database HIVsirDB of siRNAs responsible for silencing HIV genes. DESCRIPTIONS: HIVsirDB is a manually curated database of HIV inhibiting siRNAs that provides comprehensive information about each siRNA or shRNA. Information was collected and compiled from literature and public resources. This database contains around 750 siRNAs that includes 75 partially complementary siRNAs differing by one or more bases with the target sites and over 100 escape mutant sequences. HIVsirDB structure contains sixteen fields including siRNA sequence, HIV strain, targeted genome region, efficacy and conservation of target sequences. In order to facilitate user, many tools have been integrated in this database that includes; i) siRNAmap for mapping siRNAs on target sequence, ii) HIVsirblast for BLAST search against database, iii) siRNAalign for aligning siRNAs. CONCLUSION: HIVsirDB is a freely accessible database of siRNAs which can silence or degrade HIV genes. It covers 26 types of HIV strains and 28 cell types. This database will be very useful for developing models for predicting efficacy of HIV inhibiting siRNAs. In summary this is a useful resource for researchers working in the field of siRNA based HIV therapy. HIVsirDB database is accessible at http://crdd.osdd.net/raghava/hivsir/.

Giant cell tumor of the metacarpal bones.

Giant cell tumor (GCT) of hand bones is rare. We present two cases of GCT of metacarpal bone. One case was treated successfully with ray amputation. The second patient underwent wide resection and tricortical iliac crest bone grafting. Till the last follow-up (at 26 and 70 months respectively) both patients have been recurrence free and have returned to their previous occupational activities.

Giant cell tumour of bone: an analysis of 139 Indian patients.

BACKGROUND: Giant cell tumour of bone (GCT) is a benign but locally aggressive lesion. We analysed a series of GCTs of bone to determine whether there was any variation in the incidence and distribution in an Indian population compared to other populations reported in the literature, as well as treatment options applicable in developing countries, and we report the results here. METHODS: A total of 139 patients with histologically proven GCT of bone were treated in our referral centre. Of these, 124 cases had a follow-up of more than 2 years (mean 8.3 years). Demographically, 72 were male, 67 were female, and they had a mean age of 29 years (range 15-59 years). The majority of the cases were of Campanacci grade III (n = 72, 51.1%). A total of 157 oncological procedures were performed. RESULTS: Incidence of GCT of bone was found to be 20.3% (n = 139/685) among all primary bone tumours. The distal radial involvement amounted to 22.7% (n = 28). There were 14 recurrences (11.1%) and 3 re-recurrences. Functional outcome was evaluated using the MSTS-93 scoring system. Average rating was 89.6% (avg. score 26.9) for upper extremities and 84% (avg. score 25.2) for lower extremities. CONCLUSIONS: The incidence of GCT of bone was found to be high in our population, with surprisingly high involvement of the distal radius. Nonvascularised autogenous fibular graft was found to be an effective option for reconstruction. The Indian population, like their South East Asian neighbours, has a higher incidence of GCT compared to Western populations described in the literature.

Local recurrences after curettage and cementing in long bone giant cell tumor.

BACKGROUND: Giant cell tumor of bone (GCT) is a benign lesion with great propensity for local recurrence. This study aimed to analyse the rates of local recurrence and its possible predisposing factors in Campanacci's Grade III and II GCT of long bones following intralesional curettage and bone cementing. MATERIALS AND METHODS: 32 cases of either sex with Campanacci's Grade II (n= 14), and Grade III (n=18) with intact articular surface, operated between 1995 and 2007 in form of intralesional curettage and bone cementing were studied. All the cases were followed up for 2.5-12 years (mean, 6.5), after primary treatment. The mean age at operation was 32.4 years (range, 18.5-40 years). The proximal tibia was involved in 13 cases (40.6%), followed by distal femur (n=11)34.4% distal tibia (n=3) 9.4%, proximal femur (n=2) 3.2% and distal radius (n=3) 9.4%. RESULTS: Eleven patients (34.4%) had local recurrence, of which eight were of Campanacci's Grade III. The mean recurrence time was 14 months (range, 3-34 months). The two-year recurrence-free survivorship was 71.9% (n=23/32). Post-recurrence mean follow-up was 4.2 years (range, 2-6.5 years). CONCLUSION: We observed higher rate of local recurrence with Campanacci's Grade III GCTs. We recommend selective use of this procedure in Grade III lesions, particularly with extensive soft tissue involvement.

Resection-reconstruction arthroplasty for giant cell tumor of distal radius.

BACKGROUND: Giant cell tumor (GCT) of the distal radius poses problems for reconstruction after resection. Several reconstructive procedures like vascularized and non-vascularized fibular graft, osteo-articular allograft, ceramic prosthesis and megaprosthesis are in use for substitution of the defect in the distal radius following resection. Most authors advocate wrist arthrodesis following resection of distal radius and non vascularized fibular graft. Here we have analyzed the results of aggressive benign GCTs of the distal radius treated by resection and reconstruction arthroplasty using autogenous non-vascularized fibular graft. MATERIALS AND METHODS: Twenty-four cases of giant cell tumor of the distal radius (mean age 32 years, mean follow-up 6.6 years) treated by en-bloc resection and reconstruction arthroplasty using autogenous non-vascularized ipsilateral fibular graft with a minimum followup of two years have been included in this retrospective study. Nineteen cases were of Campanacci grade III and five were of Grade II recurrence. The mean resected length of the radius was 9.5 (8-12) cm. Routine radiographs and clinical assessments regarding pain, instability, recurrence, hand grip strength and functional status were done at regular intervals and functional results were assessed using (musculoskeletal tumor society) MSTS-87 scoring. RESULTS: Early radiological union at host-graft junction was achieved at mean 12.5 weeks, (range 12-14 weeks) and solid incorporation with callus formation was observed in mean 29 weeks (range 28-32 weeks) in all the cases. Satisfactory range of motion (mean 63%, range 52-78%) of the wrist was achieved in 18 cases. Grip strength compared to the contralateral hand was found to be 67% (range 58-74%). Functional results were excellent in six cases (25%), good in 14 cases (58.3%) and four (16.7%) cases had fair results. Soft tissue recurrence was seen in one patient. The most commonly encountered complication was fibulo-carpal subluxation (10 cases, 41.7%). CONCLUSION: Resection of the distal radius and reconstruction arthroplasty with non-vascularized proximal fibular graft is useful in preserving the functional movement and stability of the wrist as well as achieving satisfactory range of movement and grip strength.

Increased levels of inflammatory mediators in children and adults infected with Vibrio cholerae O1 and O139.

Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1- and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO*) metabolites (nitrite and nitrate [NO(2)(-) and NO(3)(-)]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F(2 alpha) remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE(2), LTB(4), and NO*, as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.