Seaweed biomass as a sustainable resource for synthesis of ZnO nanoparticles using Sargassum wightii ethanol extract and their environmental and biomedical applications through Gaussian mixture model.

Zinc oxide nanoparticles (ZnO) possess unique features that mak them a common matter among different industries. Nevertheless, traditional models of synthesizing ZnO-NPs are related with health and environmental and risks due to harmful chemicals. The biosynthesis of zinc oxide nanoparticles was achieved using the hot water extract of Sargassum wightii (SW), which serves as a reducing agent. This extract is mixed with zinc precursors, initiating a bio-reduction process. UV-vis, FTIR, XRD, Raman, DLS, SEM, EDX, TEM imaging, and XPS analysis are used. The novelty of this research lies in utilizing a bio-reduction process involving hot water extract of SW to synthesize zinc oxide nanoparticles, providing a safer and eco-friendly alternative to traditional chemical methods. Here, the zinc oxide nanoparticles produced through the biosynthesis process effectively addressed oral infections (Streptococcus mutans) due to their ability to disrupt the integrity of bacterial cell membranes, interfere with cellular processes, and inhibit the growth and proliferation of bacteria responsible for oral infections. Gaussian Mixture Models (GMMs) uncover intricate patterns within medical data, enabling enhanced diagnostics, treatment personalization, and patient outcomes. This study aims to apply Gaussian Mixture Models (GMMs) to medical data for subpopulation identification and disease subtyping, contributing to personalized treatment strategies and improved patient care. With a dataset comprising 300 samples, the application of GMM showed lower BIC and AIC values (2500, 3200), a high Silhouette Score (0.65 from -1 to 1) reflecting well-defined clusters, Calinski-Harabasz (120) and Davies-Bouldin Indices (0.45). These metrics collectively underscored the model's success in revealing distinct patterns within the data. ZnO-nanocoated aligners were effective against Streptococcus mutans, with the maximum antibacterial effect observed for 2 days and lasting for 7 days.

Transcriptome-guided resolution of tumor microenvironment interactions in pheochromocytoma and paraganglioma subtypes.

BACKGROUND: Pheochromocytomas and paragangliomas (PCPG) are rare catecholamine-secreting endocrine tumors deriving from chromaffin cells of the embryonic neural crest. Although distinct molecular PCPG subtypes have been elucidated, certain characteristics of these tumors have yet to be fully examined, namely the tumor microenvironment (TME). To further understand tumor-stromal interactions in PCPG subtypes, the present study deconvoluted bulk tumor gene expression to examine ligand-receptor interactions. METHODS: RNA-sequencing data primary solid PCPG tumors were derived from The Cancer Genome Atlas (TCGA). Tumor purity was estimated using two robust algorithms. The tumor purity estimates and bulk tumor expression values allowed for non-negative linear regression to predict the average expression of each gene in the stromal and tumor compartments for each PCPG molecular subtype. The predicted expression values were then used in conjunction with a previously curated ligand-receptor database and scoring system to evaluate top ligand-receptor interactions. RESULTS: Across all PCPG subtypes compared to normal samples, tumor-to-tumor signaling between bone morphogenic proteins 7 (BMP7) and 15 (BMP15) and cognate receptors ACVR2B and BMPR1B was increased. In addition, tumor-to-stroma signaling was enriched for interactions between predicted tumor-originating delta-like ligand 3 (DLL3) and predicted stromal NOTCH receptors. Stroma-to-tumor signaling was enriched for interactions between ephrins A1 and A4 with ephrin receptors EphA5, EphA7, and EphA8. Pseudohypoxia subtype tumors displayed increased predicted stromal expression of genes related to immune-exhausted T-cell response, including those for inhibitory receptors HAVCR2 and CTLA4. CONCLUSION: The current exploratory study predicted stromal and tumor through compartmental deconvolution and yielded previously unrecognized interactions and putative biomarkers in PCPG.

Mitigation policies, community mobility, and COVID-19 case counts in Australia, Japan, Hong Kong, and Singapore.

OBJECTIVES: The objective of the study was to characterize the timing and trends of select mitigation policies, changes in community mobility, and coronavirus disease 2019 (COVID-19) epidemiology in Australia, Japan, Hong Kong, and Singapore. STUDY DESIGN: Prospective abstraction of publicly available mitigation policies obtained from media reports and government websites. METHODS: Data analyzed include seven kinds of mitigation policies (mass gathering restrictions, international travel restrictions, passenger screening, traveler isolation/quarantine, school closures, business closures, and domestic movement restrictions) implemented between January 1 and April 26, 2020, changes in selected measures of community mobility assessed by Google Community Mobility Reports data, and COVID-19 epidemiology in Australia, Japan, Hong Kong, and Singapore. RESULTS: During the study period, community mobility decreased in Australia, Japan, and Singapore; there was little change in Hong Kong. The largest declines in mobility were seen in places that enforced mitigation policies. Across settings, transit-associated mobility declined the most and workplace-associated mobility the least. Singapore experienced an increase in cases despite the presence of stay-at-home orders, as migrant workers living in dormitories faced challenges to safely quarantine. CONCLUSIONS: Public policies may have different impacts on mobility and transmission of severe acute respiratory coronavirus-2 transmission. When enacting mitigation policies, decision makers should consider the possible impact of enforcement measures, the influence on transmission of factors other than movement restrictions, and the differential impact of mitigation policies on subpopulations.

PERPETRATION OF VIOLENCE BY FEMALE SEX WORKERS IN PAPUA NEW GUINEA: 'WE WILL CRUSH THEIR BONES'.

There is a small but important body of literature on female sex workers' (FSWs) violence towards others, but little of that focused on low- and middle-income countries. Drawn from a larger biobehavioural study of FSWs in three cities in Papua New Guinea, we analyse the interviews from 19 FSWs who reported having perpetrated physical violence towards four major groups: (1) ex-husbands; (2) clients; (3) other sex workers and (4) other people (mainly women). Our study demonstrates that FSWs' use of violence arises from a complex set of social, material and gendered circumstances and cannot be addressed in isolation from other aspects of their lives.

Using an orbit shield during volume perfusion CT: is it useful protection or an obstacle?

AIM: To evaluate the image quality and artefacts resulting from in-plane orbit shielding during computed tomography (CT) perfusion and to assess the possibility of artefact reduction using the iterative metal artefact reduction (iMAR) algorithm. MATERIALS AND METHODS: Twenty-eight perfusion CT examinations obtained from 20 patients using orbit shields were included in this study. Source images and perfusion maps were analysed retrospectively to detect the type and extent of artefacts. Original images were compared with images processed using the iMAR algorithm. The extent of artefacts was categorised into three groups: orbital/frontal, middle fossa, and posterior fossa. Types of artefacts in source images were categorised as noise, streak, beam hardening, or a combination of those, and types of artefacts in perfusion maps were categorised as: noise, image distortion, areas with missing colour codes, or incorrect colour-coding. RESULTS: All source images evaluated showed artefacts related to orbit shielding and 85.7% reached the posterior fossa. In 92.8% of scans, perfusion maps showed artefacts, mostly as incorrect colour codes. Of the perfusion maps with artefacts, 92.3% reached the posterior fossa. After application of the iMAR algorithm, an increase in the extent of artefacts was observed in 93% of perfusion maps, and no improvement of image quality was noted. CONCLUSION: Orbit shields cause significant artefacts if used for in-plane shielding during whole-brain CT perfusion, and render areas at the level of the shield undiagnosable. Usage of an orbit shield during whole-brain CT perfusion is not recommended, so alternative methods for reducing the radiation dose are advisable.

Methyl thiophanate-induced toxicity in liver and kidney of adult rats: a biochemical, molecular and histopathological approach.

The aim of this study was to elucidate the redox effects of Thiophanate methyl (MT) in the rat liver and kidney. Our results showed, after 3 days of MT injection (700 mg/kg), an increase in malondialdehyde (MDA), hydrogen peroxide and advanced oxidation protein products levels. Glutathione peroxidase and superoxide dismutase activities were also remarkably increased in the liver but decrease in the kidney. Glutathione and vitamin C values were significantly reduced. The changes in biochemical parameters were substantiated by histological and molecular data. A smear without ladder formation on agarose gel was shown, indicating random DNA degradation in the liver and the kidney of MT treated rats. The increase in cyclooxygenase-2 gene expression, marker of inflammation, and an increase in genes expression of glutathione peroxidase and superoxide dismutase in liver and their decrease in the kidney were also occurred after MT exposure. These data confirmed the pro-oxidant and genotoxic effects of this fungicide.

Influence of age and co-medication on the steady-state pharmacokinetics of valproic acid in Tunisian patients with epilepsy.

AIM: Valproic acid (VPA) is a widely prescribed broad-spectrum antiepileptic drug. However, the use of VPA is complicated in clinical practice by its remarkably wide variability of pharmacokinetics. The objective of this study was to investigate the effects of demographic factors and associated therapies on steady-state plasma VPA concentrations in patients with epilepsy. METHODS: This retrospective cohort study was carried out using the routine therapeutic drug monitoring (TDM) database. Stepwise logistic regression analysis was used to compare serum VPA levels in 78 epilepsy patients treated with VPA in association with at least one other drug that could have interacted with CYP2C9, CYP2C19 or UGT enzymes. RESULTS: The frequency of subtherapeutic serum VPA levels was significantly increased with younger age (P<0.02), the number of co-medications (P<0.007) and use of enzyme-inducing co-medications (P<0.02). No significant correlations between VPA dose and trough plasma concentrations were found, as the latter did not increase in proportion to the dose. CONCLUSION: Routine monitoring of VPA serum levels would be extremely useful in epilepsy patients in the pediatric age group and in those who require associated enzyme-inducing medications.

Role of Ion Kinetic Physics in the Interaction of Magnetic Flux Ropes.

To explain many natural magnetized plasma phenomena, it is crucial to understand how rates of collisionless magnetic reconnection scale in large magnetohydrodynamic (MHD) scale systems. Simulations of isolated current sheets conclude such rates are independent of system size and can be reproduced by the Hall-MHD model, but neglect sheet formation and coupling to MHD scales. Here, it is shown for the problem of flux-rope merging, which includes this formation and coupling, that the Hall-MHD model fails to reproduce the kinetic results. The minimum sufficient model must retain ion kinetic effects, which set the ion diffusion region geometry and give time-averaged rates that reduce significantly with system size, leading to different global evolution in large systems.

Ameliorative effects of vanillin on potassium bromate induces bone and blood disorders in vivo.

The objective of this study was to investigate the propensity of potassium bromate (KBrO3) to induce oxidative stress in blood and bone of adult mice and its possible attenuation by vanillin. Our results demonstrated, after KBrO3 treatment, a decrease of red blood cells and hemoglobin and a significant increase of white blood cell. A decrease in plasma levels of folic acid, vitamin B12 and iron was also noted. Interestingly, an increase of lipid peroxidation, hydroperoxides, hydrogen peroxide, advanced oxidation protein products and protein carbonyl levels in erythrocytes and bone was observed, while superoxide dismutase, catalase and glutathione peroxidase activities and glutathione, non-protein thiol and vitamin C levels were decreased. KBrO3 treatment resulted in blood and bone DNA fragmentation, a hallmark of genotoxicity-KBrO3-induced, with reduction of DNA levels. Calcium and phosphorus levels showed a decrease in the bone and an increase in the plasma after KBrO3 treatment. These biochemical alterations were accompanied by histological changes in the blood smear and bone tissue. Treatment with vanillin improved the histopathological, hematotoxic and genotoxic effects induced by KBrO3. The results showed, for the first time, that the vanillin possesses a potent protective effect against the oxidative stress and genotoxicity in bone and blood of KBrO3-treated mice.

Intraneural Ganglions of the Hand and Wrist.

PURPOSE: To review 15 patients who were treated for intraneural ganglions of the hand and wrist. METHODS: Between 1990 and 2012, 15 patients were treated for intraneural ganglions of the hand and wrist. There were 9 women and 6 men, averaged age 42 years. Ten patients presented with a mass and 5 with symptoms of entrapment neuropathy. The ganglions involved the ulnar nerve at the wrist in 5 patients, the dorsal branch of the ulnar nerve in 2, the superficial radial nerve in 2, a digital nerve in 4, and the dorsal branch of a digital nerve in 2. Eight patients had magnetic resonance imaging evaluations that showed cystic masses that did not confirm intraneural ganglions. In all patients diagnosis was made intraoperatively. Ganglions were treated by intraneural dissection and excision of the cyst in 10 patients, excision of the articular branch and decompression of the cyst in 4, and excision of the ganglion and the nerve in 1. RESULTS: Postoperative follow-up averaged 57 months. There were no complications or recurrences. Five patients had transient paresthesias that improved after an average of 2 months. Preoperative symptoms improved in all patients. Patients returned to normal daily and work activities at an average of 10 days. CONCLUSIONS: Intraneural ganglions should be considered in the differential diagnosis of a mass in the vicinity of a nerve. Surgical excision is usually curative but simple excision of the articular branch and decompression of the cyst seems simpler and equally effective. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Global dynamics and computational modeling for analyzing and controlling Hepatitis B: A novel epidemic approach.

Hepatitis B virus (HBV) infection is a global public health issue. We offer a comprehensive analysis of the dynamics of HBV, which can be successfully controlled with vaccine and treatment. Hepatitis B virus (HBV) causes a significantly more severe and protracted disease compared to hepatitis A. While it initially presents as an acute disease, in approximately 5 to 10% of cases, it can develop into a chronic disease that causes permanent damage to the liver. The hepatitis B virus can remain active outside the body for at least seven days. If the virus penetrates an individual's body without immunization, it may still result in infection. Upon exposure to HBV, the symptoms often last for a duration ranging from 10 days to 6 months. In this study, we developed a new model for Hepatitis B Virus (HBV) that includes asymptomatic carriers, vaccination, and treatment classes to gain a comprehensive knowledge of HBV dynamics. The basic reproduction number [Formula: see text] is calculated to identify future recurrence. The local and global stabilities of the proposed model are evaluated for values of [Formula: see text] that are both below and above 1. The Lyapunov function is employed to ensure the global stability of the HBV model. Further, the existence and uniqueness of the proposed model are demonstrated. To look at the solution of the proposed model graphically, we used a useful numerical strategy, such as the non-standard finite difference method, to obtain more thorough numerical findings for the parameters that have a significant impact on disease elimination. In addition, the study of treatment class in the population, we may assess the effectiveness of alternative medicines to treat infected populations can be determined. Numerical simulations and graphical representations are employed to illustrate the implications of our theoretical conclusions.

Semantic and traditional feature fusion for software defect prediction using hybrid deep learning model.

Software defect prediction aims to find a reliable method for predicting defects in a particular software project and assisting software engineers in allocating limited resources to release high-quality software products. While most earlier research has concentrated on employing traditional features, current methodologies are increasingly directed toward extracting semantic features from source code. Traditional features often fall short in identifying semantic differences within programs, differences that are essential for the development of reliable and effective prediction models. In contrast, semantic features cannot present statistical metrics about the source code, such as the code size and complexity. Thus, using only one kind of feature negatively affects prediction performance. To bridge the gap between the traditional and semantic features, we propose a novel defect prediction model that integrates traditional and semantic features using a hybrid deep learning approach to address this limitation. Specifically, our model employs a hybrid CNN-MLP classifier: the convolutional neural network (CNN) processes semantic features extracted from projects' abstract syntax trees (ASTs) using Word2vec. In contrast, the traditional features extracted from the dataset repository are processed by a multilayer perceptron (MLP). Outputs of CNN and MLP are then integrated and fed into a fully connected layer for defect prediction. Extensive experiments are conducted on various open-source projects to validate CNN-MLP's effectiveness. Experimental results indicate that CNN-MLP can significantly enhance defect prediction performance. Furthermore, CNN-MLP's improvements outperform existing methods in non-effort-aware and effort-aware cases.

ATME-Needs, requirements and cross-sectoral patient journeys of patients with out-of-hospital mechanical ventilation and intensive care in outpatient settings: study protocol for an observational study.

INTRODUCTION: An increasing number of tracheotomised and/or ventilated patients with high-cost out-of-hospital intensive care needs and, at the same time, a decreasing number of healthcare professionals inevitably lead to challenges in the care of this patient population. In addition, little is known about this population, their health restrictions, needs, patient journeys, care structures and processes. The project 'Needs, requirements and cross-sectoral care pathways of out-of-hospital ventilated intensive care patients' (ATME) aims to analyse these aspects and explore current care structures to inform further development of care in line with patients' needs and requirements. METHODS AND ANALYSIS: Qualitative and quantitative methods will be used. In preparation of a semistandardised survey, exploratory interviews will be conducted with tracheotomised and/or ventilated patients with out-of-hospital intensive care needs (TVPOI) (n=15), nursing care providers (n=30), outpatient medical centres, as well as outpatient medical, medical technology and therapeutic care providers (n=35). Three semistandardised survey questionnaires for TVPOI (n=2,000) will be developed and conducted with nursing care facilities (n=250) and outpatient medical centres for mechanical ventilation (n=25). Content analyses will be conducted for qualitative data; survey data will be analysed descriptively. In addition, healthcare claims data will be analysed descriptively to provide information on patient journeys. Three result workshops and one consensus conference will be carried out with representatives of the relevant target groups to analyse the suitability of care structures and to develop recommendations for action to improve TVPOI. ETHICS AND DISSEMINATION: The ATME study received a positive vote from the Ethics Committee of the Osnabrück University of Applied Sciences and is registered in 'Deutsches Register Klinischer Studien (DRKS)' (registration number: DRKS00030891). The study results will be presented at national conferences and in relevant peer-reviewed journals. Additionally, study results will be published by the funding institution (the Innovation Committee of the Federal Joint Committee) on their website.

The level and distribution of selected organochlorine pesticides in water of River Satluj Pakistan.

The study was aimed to identify different environmental factors (selected organochlorine pesticides) affecting the river water of Satluj. River Sutlej is about 1400 kilometers long and its water is extensively used for irrigation in Punjab, located both in India and Pakistan, which was also a reason of dispute between both countries for its water share. The study area was divided into four zones, Sulemanki Zone, Islam Zone, Mailsi Syphone Zone and Panjnad Zone. Liquid Liquid Extraction (LLE) technique was used for the collected water samples followed by high performance liquid chromatography (HPLC) UV-Visible detector The current finding revealed that aldrin was not detected during summer period in water samples of SZ-1 (Sulemanki Barrage), SZ-2 and SZ-3 (Maisli Siphon) of the study area. Lindane and DDE were found more in the samples of sediments from the study area at SZ-4 ranging from 2.238-8.226 ppb and 4.234-6.876 ppb, respectively. Heaptachlor (in sediments) was found to be0.032-234 ppb only at SZ-4.Endosulfan concentrations in water (winter) at SZ-3 was 0.06 ppb and at SZ-4,it was 0.05 ppb; dieldrin in water (winter) at SZ-4 was 0.0314 ppb and heptachlor was detected at SZ-1 (0.0315 ppb) and SZ-2 (0.0310 ppb) in water during winter season, were reaching to the Maximum Concentrations Limits (MCL), while all other residues investigated were found below the MCLin all the compartments of the study area set by various agencies like WHO/FAO- Codex Alimenterious. Present findings revealed that although the organochlorine pesticides are banned for agricultural use in many countries, including Pakistan, their presence in various samples might be due to illegal use of these pesticides in the study area and its neighboring regions. The overall study area comprises of mainly urban, suburban and agricultural land being the largest cotton growing area of the country. There is a need to take serious steps to minimize water pollution caused by pesticides to achieve a healthy lifestyle.

Genomic Analyses of Germline and Somatic Variation in High-Grade Serous Ovarian Cancer.

Background High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 577 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations. Results Approximately one-third of tumors had loss-of-function germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM , and PALB2 . Loss-of-function germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP , and NF1 . In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of loss-of-function variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536 , and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. Conclusions From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 577 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.

Genomic analyses of germline and somatic variation in high-grade serous ovarian cancer.

BACKGROUND: High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 557 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations (SCNA). RESULTS: Approximately one-third of tumors had loss-of-function (LOF) germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM, and PALB2. LOF germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP, and NF1. In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of LOF variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536, and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. CONCLUSIONS: From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.

Coexistence of sickle cell disease and severe congenital neutropenia: first impressions can be deceiving.

We report an Omani family in whom the propositus had a rare coexistence of sickle cell disease and severe congenital neutropenia associated with a mutation in ELANE. In contrast to his siblings with sickle cell disease, the severity of HbSS-associated complications such as painful crises and acute chest syndrome was significantly reduced. His course of the disease had markedly worsened after initiating G-CSF therapy. These clinical observations suggest that neutropenia may ameliorate inflammatory responses and thus display a modulating factor with respect to the clinical course of sickle cell disease.

Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatotoxicity in Tunisian patients with tuberculosis.

SETTING: Antituberculosis drug-induced hepatitis attributed to isoniazide (INH) is one of the most prevalent drug-induced liver injuries. INH is metabolized by hepatic N-acetyltransferase 2 (NAT2) to form hepatotoxins. AIM: To evaluate whether polymorphism of the NAT2 gene was associated with antituberculosis drug-induced hepatotoxicity in Tunisian patients. METHODS: A total of 66 patients with tuberculosis (TB) who received anti-TB treatment were followed prospectively. Their NAT2 genotype was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We identified three single nucleotide polymorphisms (SNPs); 481C to T (NAT2*5B), 590G to A (NAT2*6A) and 857G to A (NAT2*7B). Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. RESULTS: Fourteen patients (21.2%) were diagnosed with anti-TB drug-induced hepatitis. None of the rapid acetylators-type patients have expressed serum aminotransferase elevation. Among patients with hepatotoxicity, slow acetylators-type patients had a higher risk of hepatotoxicity than intermediate acetylators (21.4% vs. 78.6%, P=0.01). Statistical analysis revealed that the frequency of a variant diplotypes, NAT2*5B/5B and NAT2*6A/6A, were significantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity (P=0.01, odds ratio [OR]=7.6 and P=0.029, OR=15, respectively). By contrast, the frequency of the rapid acetylation NAT2*4 allele was significantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P=0.02, OR=0.18). Moreover, 590G/G genotype was associated with decreased hepatotoxicity (P=0.01); by contrast, homozygous point mutation at position 481 and 590 were associated with a higher risk of hepatotoxicity (P=0.01). CONCLUSION: Our results suggest that the slow-acetylator status of NAT2 is risk factor for INH-induced hepatotoxicity. Moreover, diplotypes, NAT2*5B/5B, NAT2*6A/6A, 481T/T and 590A/A, are useful new biomarkers for predicting anti-TB drug-induced hepatotoxicity.

Functional outcome of open reduction of chronic perilunate injuries.

PURPOSE: Perilunate injuries are complex and occasionally go unrecognized acutely. Open reduction and internal fixation is a valid treatment option for these injuries. The purpose of this study was to evaluate the functional outcome of treating chronic perilunate injuries with open reduction and internal fixation. METHODS: Between 1998 and 2007, we treated 24 patients for chronic perilunate injuries. We excluded 5 patients from this study because they underwent proximal row carpectomy or limited wrist arthrodesis. We treated the remaining 19 patients with open reduction and internal fixation. Mean time from injury to surgery was 29 weeks. All patients were men, with a mean age of 27 years. A total of 13 patients had fracture dislocations (group 1); of these, 11 were transscaphoid and 2 were transscaphoid transcapitate fracture dislocations. Six patients had perilunate dislocations (group 2). RESULTS: Postoperative follow-up averaged 58 months. All carpal fractures healed at an average of 18 weeks. At final evaluation, the average pain scores during rest, daily activities, and manual work on a 20-point visual analog scale were 0, 2, and 3, respectively, with no significant difference between groups. The active extension and flexion of the wrist averaged 39% and 52% of the uninjured side, respectively. Grip strength averaged 87% of the uninvolved extremity. According to the Mayo wrist scoring system, 58% of all patients (69% of group 1 and 33% of group 2) achieved good to excellent results. A total of 18 patients returned to their original work activities; 14 patients (74%) were very satisfied. No patients required secondary procedures. CONCLUSIONS: Despite late presentation, patients with chronic perilunate injuries can be treated with open reduction internal fixation, with satisfactory results. Patients with lesser arc injuries have less successful outcome. Patients with irreducible dislocations or major articular damage may require wrist salvage procedures.