Global gross nitrification rates are dominantly driven by soil carbon-to-nitrogen stoichiometry and total nitrogen.

Soil gross nitrification (GN) is a critical process in the global nitrogen (N) cycle that results in the formation of nitrate through microbial oxidation of ammonium or organic N, and can both increase N availability to plants and nitrous oxide emissions. Soil GN is thought to be mainly controlled by soil characteristics and the climate, but a comprehensive analysis taking into account the climate, soil characteristics, including microbial characteristics, and their interactions to better understand the direct and indirect controlling factors of GN rates globally is lacking. Using a global meta-analysis based on 901 observations from 330 15 N-labeled studies, we show that GN differs significantly among ecosystem types, with the highest rates found in croplands, in association with higher pH which stimulates nitrifying bacteria activities. Autotrophic and heterotrophic nitrifications contribute 63% and 37%, respectively, to global GN. Soil GN increases significantly with soil total N, microbial biomass, and soil pH, but decreases significantly with soil carbon (C) to N ratio (C:N). Structural equation modeling suggested that GN is mainly controlled by C:N and soil total N. Microbial biomass and pH are also important factors controlling GN and their effects are similar. Precipitation and temperature affect GN by altering C:N and/or soil total N. Soil total N and temperature drive heterotrophic nitrification, whereas C:N and pH drive autotrophic nitrification. Moreover, GN is positively related to nitrous oxide and carbon dioxide emissions. This synthesis suggests that changes in soil C:N, soil total N, microbial population size, and/or soil pH due to anthropogenic activities may influence GN, which will affect nitrate accumulation and gaseous emissions of soils under global climate and land-use changes.

Validation of a 15-gene hypoxia classifier in head and neck cancer for prospective use in clinical trials.

BACKGROUND: In head and neck squamous cell carcinomas (HNSCC) hypoxic radioresistance can be reduced by use of the hypoxic modifier nimorazole, as shown in the DAHANCA 5 trial. Recently, a 15-gene hypoxia classifier has shown predictive impact for the effect of nimorazole by identifying 'more' and 'less' hypoxic tumors in the DAHANCA 5 cohort. A prospective multicentre EORTC-1219 study is initiated, where nimorazole and prospective use of the classifier as a predictor is tested in relation to the most recent accelerated chemoradiotherapy treatment. Validation of the gene expression classification procedures is described here. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor material from three recent HNSCC cohorts [DAHANCA 18 (n = 96), 24 (n = 40), and IAEA Hypo (n = 55)] was used to establish and validate procedures for prospective classification of patients. Repeatability was tested for the different steps in the gene expression analysis, and reproducibility was tested with xenograft tumors (FaDuDD, UTSCC33), where gene expression in complementary sections was compared after fixation and embedding locally and at international institutions, respectively. Intra-tumor heterogeneity was addressed by classifying biopsy samples from HNSCC tumors, where 2-4 biopsies from each tumor was accessible. RESULTS: Procedures were successfully established for individual classification of HNSCC patients in retrospective and prospective cohorts. Measurements of gene expression levels were reproducible between different international institutions. CONCLUSION: Technical validation of the 15-gene hypoxia classifier demonstrated that it is suitable for implementation in prospective clinical trials.

Compliance and toxicity of the hypoxic radiosensitizer nimorazole in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).

PURPOSE: To evaluate the compliance and toxicity of the hypoxic radiosensitizer nimorazole in head and neck cancer patients. METHODS: A retrospective study of patients with head and neck squamous cell carcinoma (HNSCC), treated in Denmark between 1990 and 2013. All patients treated with radical radiotherapy (± chemotherapy) [66-70 Gy; 33-35 fractions; 2 Gy/fraction; 5-6 fractions/week] concomitant with the hypoxic radiosensitizer nimorazole. Nimorazole was administered as oral tablets in doses of approximately 1.2 g/m(2) body surface area in connection with the first of each daily radiation treatment. A second daily dose of 1 g was given in connection with the second radiotherapy fraction in the accelerated fractionation regimen. The compliance was estimated as the percentage of the initially prescribed dose, which was received by each patient. The main side effects were recorded. RESULTS: A total of 1049 patients were investigated. The tolerance to nimorazole was fair: 58% of patients received the full prescribed total dose. Nausea and vomiting were the major complaints: among the 260 patients with dose reductions due to known side effects, (87%) were due to nausea/vomiting. All side effects ceased when treatment was interrupted, and neither severe nor long lasting side effects were observed. Female patients were significantly more likely to have dose reduction (OR 2.02; 95% CI 1.50-2.70), and nausea/vomiting. Patients aged more than 70 years were significantly more likely to have dose reduction. Patients who received less than 1100 mg/m(2) were significantly less likely to have dose reduction (OR 0.58; CI 0.44-0.78), and nausea/vomiting, compared to those who received 1100-1300 mg/m(2). The tolerance was also less in the group of patients received accelerated chemoradiotherapy (OR 1.70; CI 1.20-2.50) with more association with nausea/vomiting (OR 2.09; CI 1.40-3.10). CONCLUSION: The compliance to nimorazole is fair, with tolerable acute, but neither persistent nor late, toxicity. It can be administered with chemotherapy and different radiotherapy fractionation schedules.

Impact of green antioxidants on decreasing the aflatoxins percentage in peanut oil seed (Arachis hypogaea L.) during storage.

The present study conducted an experimental investigation to impede the degradation of peanut (Arachis hypogaea L.) seeds and enhance their quality while being stored. The efficacy of eco-friendly chemicals such as ascorbic acid, salicylic acid, acetic acid, and propionic acid in seed preservation was evaluated over a period of six months. After a period of six months of storage in a greenhouse, an examination was conducted on peanut seeds that had undergone treatment. Rhizoctonia was observed after Cephalothorax, whereas Aspergillus, Fusarium, and Penicillium were the prevailing fungi throughout the storage period. The optimal outcomes were obtained from the conversion of acetic acid to propionic acid. The study observed a decline in seed oil, protein, carbohydrates, germination percentage, energy, index, length, vigour index, dead and rotten seeds, rotted seedlings, and surviving healthy seedlings, with an increase in storage duration ranging from zero to six months. The application of 100% propionic acid to peanut seeds throughout the storage duration resulted in decreased occurrences of deceased seeds, decaying seeds, and deteriorated seedlings. Peanut seeds that underwent treatment with green chemical agents of moderate and high intensity were found to be free of aflatoxin B1. The highest levels of chlorophylls a and b, carotenoids, and total phenols were observed in seeds stored in greenhouses and treated with 100% propionic acid and acetic acid extract. The application of propionic acid 100%, acetic acid 100%, salicylic acid 4 g/l and ascorbic acid 4 g/l proved to be the most effective treatments for peanut seeds, exhibiting the lowest total aflatoxin level of 0.40. The correlation coefficient between shoot fresh weight and shoot dry weight was found to be 0.99, whereas the correlation coefficient between root dry weight and shoot length was 0.67. The seed chemical analysis, seedling characteristics, and germination characteristics were subjected to clustering analysis, resulting in the formation of two distinct groups. The first group consisted of germination percentage and energy levels across all time points (0-6 months), while the second group consisted of the remaining characteristics. The findings of this research propose the utilisation of 100% propionic acid as a viable method for preserving peanut seeds and preventing their deterioration during storage. The application of 100% acetic acid has been found to be effective in enhancing the quality of seeds and minimising losses.

Interplay of silymarin and clove fruit extract effectively enhances cadmium stress tolerance in wheat (Triticum aestivum).

Introduction: Osmoprotectant supplementation can be used as a useful approach to enhance plant stress tolerance. However, the effect of silymarin and clove fruit extract (CFE) on wheat plants grown under cadmium (Cd) stress has not been studied. Methods: Wheat seeds were planted in plastic pots filled with ions-free sand. A ½-strength Hoagland's nutrient solution was used for irrigation. Pots were treated with eight treatments thirteen days after sowing: 1) Control, 2) 0.5 mM silymarin foliar application [silymarin], 3) 2% CFE foliar application [CFE], 4) CFE enriched with silymarin (0.24 g silymarin L-1 of CFE) [CFE-silymarin], 5) Watering wheat seedlings with a nutritious solution of 2 mM Cd [Cd]. 6) Cadmium + silymarin, 7) Cadmium + CFE, and 8) Cadmium + CFE-silymarin. The experimental design was a completely randomized design with nine replicates. Results and discussion: The Cd stress decreased grain yield, shoot dry weight, leaf area, carotenoids, chlorophylls, stomatal conductance, net photosynthetic rate, transpiration rate, membrane stability index, nitrogen, phosphorus, and potassium content by 66.9, 60.6, 56.7, 23.8, 33.5, 48.1, 41.2, 48.7, 42.5, 24.1, 39.9, and 24.1%, respectively. On the other hand, Cd has an Application of CFE, silymarin, or CEF-silymarin for wheat plants grown under Cd stress, significantly improved all investigated biochemical, morphological, and physiological variables and enhanced the antioxidant enzyme activities. Applying CFE and/or silymarin enhanced plant tolerance to Cd stress more efficiently. Our findings suggest using CFE-silymarin as a meaningful biostimulator for wheat plants to increase wheat plants' tolerance to Cd stress via enhancing various metabolic and physiological processes.

Prophylactic cyanoacrylate injection for gastric extension of esophageal varices: a randomized controlled trial.

Aim of the study: Gastric variceal bleeding is more severe and fatal than esophageal bleeding. Injection of cyanoacrylate into bleeding gastric varices is recommended, but prophylactic injection is debatable. Aim of this study is to evaluate prophylactic cyanoacrylate injection into gastric extension of esophageal varices type 2 (GOV2). Material and methods: This randomized controlled trial included 75 patients (3 groups) with risky or bleeding esophageal varices and non-bleeding GOV2. Group A received a cyanoacrylate GOV2 injection, esophageal variceal band ligation (EBL), and ß-blocker (BB); group B received EBL and BB; and group C received EBL. Follow-up for ≥ 24 weeks to check for bleeding or death was performed. Results: Baseline variables were comparable among the 3 groups. During follow-up (median, 37.5 weeks), increasing gastric extension and or bleeding risk signs were significantly lower in group A (0%) than B (12%) and C (32%) (p < 0.001). Bleeding occurred more in groups B (24%) and C (24%) than in A (8%) (p = 0.2). Gastric extension size was an independent predictor of bleeding (p = 0.03). Portal hypertensive gastropathy (PHG) decreased in groups A (24%) and B (24%) more than in C (8%) (p = 0.5). Mortality rates were 0.0% in group A, 8% in B, and 4% in C (p = 0.2). Conclusions: Prophylactic cyanoacrylate injection into GOV2 before EBL significantly decreased the varix size and risk signs for bleeding with a statistically insignificant tendency to decrease the bleeding rate. A large gastric extension was an independent predictor of bleeding. Adding ß-blockers can potentially decrease PHG and bleeding risk. An independent study with a larger sample size is recommended to confirm the rate of bleeding and test the mortality difference.

Egyptian Consensus on the Role of Lung Ultrasonography During the Coronavirus Disease 2019 Pandemic.

Background & Aims: Coronavirus disease 2019 (COVID-19) is a global health problem, presenting with symptoms ranging from mild nonspecific symptoms to serious pneumonia. Early screening techniques are essential in the diagnosis and assessment of disease progression. This consensus was designed to clarify the role of lung ultrasonography versus other imaging modalities in the COVID-19 pandemic. Methods: A multidisciplinary team consisting of experts from different specialties (ie, pulmonary diseases, infectious diseases, intensive care unit and emergency medicine, radiology, and public health) who deal with patients with COVID-19 from different geographical areas was classified into task groups to review the literatures from different databases and generate 10 statements. The final consensus statements were based on expert physically panelists' discussion held in Cairo July 2021 followed by electric voting for each statement. Results: The statements were electronically voted to be either "agree," "not agree," or "neutral." For a statement to be accepted to the consensus, it should have 80% agreement. Conclusion: Lung ultrasonography is a rapid and useful tool, which can be performed at bedside and overcomes computed tomography limitations, for screening and monitoring patients with COVID-19 with an accepted accuracy rate.

Management of liver disease patients in different clinical situations during COVID-19 pandemic.

Chronic liver diseases are common worldwide, especially in developing countries. The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) leads to the infection of many patients with underlying chronic liver diseases. As a relatively new disease, management of COVID-19, in the context of chronic liver disease, is mainly based on the experience of the treating physician and the available data. In this review, we summarize the available evidence about the management of liver disease patients, in the context of COVID-19 infection, which can increase the severity of viral hepatitis B. Also, its clearance in HBV patients is delayed. A sixfold increased severity of COVID-19 was reported in obese patients with metabolic associated fatty liver disease (MAFDL). In patients with autoimmune liver disease (AILD), it is not recommended to change their immunosuppressive therapy (as long as they are not infected with COVID-19), in order to avoid a flare of liver disease. However, immunosuppressant drugs should be modified, in the case of infection with COVID-19. To date, no data suggest an increased risk or severity in metabolic liver diseases, such as hemochromatosis, Wilson's disease, or alpha-1 antitrypsin deficiency. Patients with liver cirrhosis should be carefully managed with minimum exposure to healthcare facilities. Basic investigations for follow-up can be scheduled at wider intervals; if patients need admission, this should be in COVID-19-clean areas. Patients with hepatocellular carcinomas may have a poor prognosis according to preliminary reports from China. The course of COVID-19 in liver transplant recipients on immunosuppression seems to have a benign course, based on few reports in children and adults. The hepatotoxicity of COVID-19 drugs ranges from mild liver enzyme elevation to a flare of underlying liver diseases. Therefore, the decision should be customized. Telemedicine can minimize the exposure of healthcare workers and patients to infection with COVID-19 and decrease the consumption of personal protective equipment.

Utility of Lung Ultrasound in Decision-making to Prioritize Hospital Admission for COVID-19 Patients: A Developing Country Perspective.

BACKGROUND AND AIMS: In the midst of this pandemic, planning the prioritization of hospital admissions for patients affected with COVID-19 should be of prime concern, particularly in healthcare settings with limited resources. Thus, in this study, we aimed to develop a novel approach to triage COVID-19 patients and attempt to prioritize their hospital admission using Lung Ultrasonography (LUS). The efficacy of LUS in triaging suspected COVID-19 patients and assessing the severity of COVID-19 pneumonia was evaluated; the findings were then compared with those obtained by chest computed tomography (CT). METHODS: This multicenter, cross-sectional study comprised 243 COVID-19 patients who presented to the emergency department in 3 major university hospitals in Egypt. LUS was performed by an experienced emergency or chest physician, according to the local protocol of each hospital. Demographic, clinical, and laboratory data were then collected from each patient. Each patient was subjected to chest CT scans and LUS. RESULTS: The mean age of the 243 patients was 46.7 ± 10.4 years. Ground-glass opacity, subpleural consolidation, translobar consolidation, and crazy paving were reported in the chest CT scans of 54.3%, 15.2%, 11.1%, and 8.6% of the patients, respectively. B-line artifacts were observed in 81.1% of the patients (confluent pattern, 18.9%). The LUS findings completely coincided with the CT findings (Kappa agreement value, 0.77) in 197 patients (81.1%) and offered a diagnostic sensitivity of 74%, diagnostic specificity of 97.9%, positive predictive value of 90.2%, and negative predictive value of 93.6% for the COVID-19 patients. Following the addition of O2 saturation to the lung imaging findings, the ultrasound method was able to demonstrate 100% sensitivity and specificity in accurately differentiating between severe and non-severe lung diseases. CONCLUSION: LUS with oxygen saturation might prove to be effective in prioritizing the hospital admission of COVID-19 patients, particularly in healthcare settings with limited resources.

Jugular pacing lead extraction with laser sheath: a case report.

Over the past 20 years, the number of patients with pacemakers (PM) or implantable cardioverter defibrillators has risen markedly; consequently, an increasing number of lead-removal procedures have become necessary. A 64-year-old woman presenting with an infected device pocket and positive bacterial cultures (Staphylococcus aureus) was admitted to our department for lead removal; in 1991, she underwent VVI PM implantation for atrioventricular II degree Mobitz 1 block, and a unipolar lead was introduced via the left jugular vein. The procedure was performed in our Electrophysiology Lab with a cardiac surgeon on standby, using an excimer laser system emitting the energy at the tip of a flexible, fibre-optic 12 F sheath, developed by Spectranetics, Inc., Colorado Springs, CO, USA.

Prospective study of prevalence and risk factors for hepatitis C in pregnant Egyptian women and its transmission to their infants.

AIM: To estimate the hepatitis C virus (HCV) vertical transmission rate, the effect of potential risk factors, and the pattern of HCV antibody response and viremia in HCV-infected infants in Benha, Egypt. METHODS: A total of 1224 pregnant women who were treated at Benha University Hospital, Egypt, were included in the study. They completed a questionnaire about risk factors for HCV acquisition and suspected risk factors for mother-to-infant transmission and were tested for HCV antibody using a third-generation ELISA test. Women positive for HCV antibody were tested for HCV RNA by polymerase chain reaction. Peripheral blood of infants of positive HCV-RNA women was tested for HCV antibody and HCV-RNA at 1 and after 6 months of age. RESULTS: Out of 1224 pregnant women, 105 (8.6%; 95% confidence interval, 7.05-10.17) were positive for HCV antibody. Only 83 (6.8%; 5.39-7.21) were positive for HCV-RNA. HCV infection was associated with older age (1.16; 1.1-1.2, P=0.001), blood transfusion (2.69; 1.2-6.0, P=0.016), and HCV infection of the husband (5.47; 1.4-21, P=0.014) or other household members (2.29; 1.2-4.6, P=0.019). Out of 53 infants tested at first month, 43 (81%; 71-92%) were positive for HCV antibody, but only 7 (13%; 4.1-22%) were positive for HCV-RNA. After 6 months, only 2 (3.8%; 0-8.95%) remained positive for HCV RNA. CONCLUSIONS: The prevalence of HCV in pregnant women in Egypt is lower than previously reported and the potential risk factors associated with HCV infection suggest intra-familial transmission. The frequency of vertical transmission of HCV in Egypt is not substantially different from other countries and does not play a role in the high prevalence of HCV in Egypt.

Critical flickering frequency test: a diagnostic tool for minimal hepatic encephalopathy.

BACKGROUND: Minimal hepatic encephalopathy (MHE) is underestimated. It affects 30-55% of patients with liver cirrhosis and can change their daily functions. Psychometric tests are sensitive in diagnosing MHE, but interpretation is difficult. Availability of a simpler diagnostic tool for MHE is mandatory. Critical flicker frequency (CFF) is a simple diagnostic test. AIM: The aim of this study was to assess the diagnostic accuracy of CFF test for MHE. PATIENTS AND METHODS: A total of 86 patients with cirrhosis with negative history of overt hepatic encephalopathy were included. History, clinical examination, laboratory investigations, and abdominal ultrasonography data were collected. Arabic version of number connection test, serial dotting test, and line tracing test were done. Total psychometric hepatic encephalopathy score (PHES) was used to diagnose MHE. CFF was done for all patients with MHE diagnosis at 39 Hz. RESULTS: Of the 86 patients, 45 (52.3%) had MHE with PHES. Patients with MHE had significantly older age, presentation with jaundice, ascites, lower hemoglobin level, lower serum albumin, prolonged INR, higher Child class and score (P≤0.001), and higher model of end stage liver disease score (P=0.001) than patients without MHE. In comparison with PHES, CFF has a sensitivity of 91.1±8.32%, specificity of 92.7±7.96%, positive predictive value of 93.2±7.44%, and negative predictive value of 90.4±8.91%. In receiver operating characteristic curve, CFF is excellent in diagnosis of MHE, with area under the curve 0.937 (P<0.001). CONCLUSION: MHE is common among patients with liver cirrhosis. CFF is a simple, rapid, noninvasive test for diagnosis of MHE, with a very good accuracy at 39 Hz.

Role of intrafamilial transmission in high prevalence of hepatitis C virus in Egypt.

BACKGROUND: Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Although an effective HCV treatment program has been adopted, it is estimated that the number of newly reported cases in Egypt is still high. Intrafamilial transmission may play a role in the high prevalence of HCV in Egypt. Identification of risk factors for the transmission of HCV may help in decreasing its prevalence and eliminating its infection. AIM: The aim of this study was to estimate the prevalence of HCV infection among the household contacts of HCV patients and identify the possible risk factors associated with intrafamilial transmission. METHODS: This study was designed as a cohort study of 90 families of patients with confirmed chronic HCV and 38 families of non-HCV-infected persons. Diagnosis of HCV infection was performed by detection of HCV antibodies by fourth-generation enzyme-linked immunosorbent assay and confirmed by HCV RNA polymerase chain reaction. A pre-prepared questionnaire on risk factors was filled out by the participants. The prevalence of HCV was calculated, and univariate and multivariate analyses were carried out to identify the independent risk factors. RESULTS: Among 90 positive-index families, 32 (35.6%) had contact persons with HCV infection compared to two of 38 (5.3%) negative-index families (P < 0.001, odds ratio [OR] = 9.9). Out of 257 index-positive contacts, 38 (14.8%) were infected compared to three of 75 (4%) of index-negative contacts (P = 0.01, OR = 4.3). Infection was associated with older age (6.9% of those aged <20 years, 10.4% of those aged 20-39 years, and 22% of those aged ≥40 years were infected) (P = 0.007). Husbands of infected wives were at a higher risk (33% infected) than wives (13.5%) and sons (16.9%) (P < 0.001). A history of hepatic encephalopathy was the independent predictor of intrafamilial transmission (P < 0.001, OR = 5.4). CONCLUSION: Intrafamilial transmission was found to possibly play a major role in the high prevalence of HCV in Egypt. Transmission was associated with older age and contact with patients with hepatic encephalopathy and was high among husbands of infected wives.

IAEA-HypoX. A randomized multicenter study of the hypoxic radiosensitizer nimorazole concomitant with accelerated radiotherapy in head and neck squamous cell carcinoma.

PURPOSE: To test the hypothesis that radiotherapy (RT) of head and neck squamous cell carcinoma (HNSCC) can be improved by hypoxic modification using nimorazole (NIM) in association with accelerated fractionation. MATERIALS AND METHODS: The protocol was activated in March 2012 as an international multicenter randomized trial in patients with HNSCC. Tumors were treated to a dose of 66-70Gy, 33-35 fractions, 6 fractions per week. NIM was administered in a dose of 1.2gperm(2), 90min before the first daily RT fraction. The primary endpoint was loco-regional failure. The trial was closed prematurely by June 2014 due to poor recruitment. An associated quality assurance program was performed to ensure the consistency of RT with the protocol guidelines. RESULTS: The trial was dimensioned to include 600 patients in 3years, but only 104 patients were randomized between March 2012 and May 2014 due to the inability to involve three major centers and the insufficient recruitment rate from the other participating centers. Twenty patients from two centers had to be excluded from the analysis due to the unavailability of the follow-up data. Among the remaining 84 patients, 82 patients were evaluable (39 and 43 patients in the RT+NIM and the RT-alone arms, respectively). The treatment compliance was good with only six patients not completing the full planned RT course, and 31 patients (79%) out of 39 allocated for NIM, achieving at least 90% of the prescribed drug dose. At the time of evaluation, 40 patients had failed to achieve persistent loco-regional tumor control, and a total of 45 patients had died. The use of NIM improved the loco-regional tumor control with an 18month post-randomization cumulative failure rate of 33% versus 51% in the control arm, yielding a risk difference of 18% (CI -3% to 39%; P=0.10). The corresponding values for overall death was 43% versus 62%, yielding a risk difference of 19% (CI -3% to 42%; P=0.10). Sixteen patients, out of 55 patients analyzed for hypoxic gene expression, were classified as having more hypoxic tumors. Such patients, if treated with RT alone, had a higher loco-regional tumor failure rate as compared to the rest of the patients with known hypoxic status (P=0.05). CONCLUSION: Although the trial was incomplete and suffered from a small number of patients, the results suggested an improvement in loco-regional tumor control and overall survival in patients with advanced HNSCC given the hypoxic modifier NIM in addition to accelerated fractionation RT. However, the trial also revealed that conducting multicenter and multinational study combining drug and RT in developing countries may suffer from uncontrolled and unsolvable problems.

Comparison of the VERSANT HCV RNA qualitative assay (transcription-mediated amplification) and the COBAS AMPLICOR hepatitis C virus test, version 2.0, in patients undergoing interferon-ribavirin therapy.

Hepatitis C virus (HCV)-infected patients were tested for the presence of HCV RNA using two qualitative assays at various time points during interferon-ribavirin therapy. Among patients treated for 48 weeks, transcription-mediated amplification and the COBAS AMPLICOR Hepatitis C Virus Test results at Week 24 predicted subsequent virologic non-response or virologic relapse in 12/15 (80%) and 8/15 (53%) patients, respectively.

Synthesis and antimicrobial activity of some new thiazole, thiophene and pyrazole derivatives containing benzothiazole moiety.

In an attempt to find a new class of antimicrobial agents, a series of thiazole, thiophene, pyrazole and other related products containing benzothiazole moiety were prepared via the reaction of N-(benzothiazol-2-yl)-2-cyanoacetamide (1) with appropriate chemical reagents. These compounds were screened for their antibacterial activity against gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes), gram-negative bacteria (Pseudomonas phaseolicola and Pseudomonas fluorescens) and antifungal activity against Fusarium oxysporum and Aspergillus fumigatus. Among the synthesized compounds, thiophene 13 showed equal activity with chloroamphenicol against S. aureus (MIC 3.125 microg/mL), while its activity was 50% lower than of chloroamphenicol against S. pyogenes. Thiazole 3 and pyrazolo[1,5-a]pyrimidine 21 b were found to exhibit the most potent in vitro antifungal activity with MICs (6.25 microg/mL) against A. fumigatus and F. oxysporum. Structures of the newly synthesized compounds were established by elemental analysis and spectral data.

Enaminonitrile in heterocyclic synthesis: synthesis and antimicrobial evaluation of some new pyrazole, isoxazole and pyrimidine derivatives incorporating a benzothiazole moiety.

Enaminonitrile 2 was used as key intermediate for the synthesis of polyfunctionally substituted heterocycles (e.g. pyrazoles, isoxazole, pyrimidines, thiazolo[3,2-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, pyrido[1,2-a]pyrimidine, 1,5-benzodiazepine, and pyrazolo[1,5-a]pyrimidine) incorporating benzothiazole moiety via its reactions with some N-nucleophiles. The newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral studies. Representative compounds of the synthesized products were tested and evaluated as antimicrobial agents.

Predictors and noninvasive identification of severe liver fibrosis in patients with chronic hepatitis C.

Diagnosis of severe fibrosis (stages III and IV) in hepatitis C has clinical implications. Our objective was to distinguish independent predictors of severe fibrosis and use them to identify patients with severe fibrosis without a liver biopsy. One hundred ninety-nine hepatitis C patients were included in the initial analysis to identify predictors of severe fibrosis. Univariate and multivariate analyses of 26 predetermined variables for significance in predicting severe fibrosis were performed. Based on the coefficient regression and P values, a scoring system was developed and applied to a second independent cohort (137 patients) for validation. In multivariate analysis, low platelet count, low albumin, aspartate transaminase level, history of blood transfusion, and hepatitis B core antibody were significant independent predictors of severe fibrosis. A scoring system (range, 0-9) was developed from the three variables with the lowest P values (platelet count, aspartate transaminase, and albumin). A cutoff point of 4 had 99% specificity and 94% positive predictive value. A cutoff point of 2 had 87% sensitivity and 95% negative predictive value. We conclude that severe fibrosis in hepatitis C may potentially be identified with a high degree of certainty in a substantial number of patients with a simple noninvasive scoring system.

Clinical significance of hepatic iron deposition and serum iron values in patients with chronic hepatitis C infection.

OBJECTIVES: To assess the potential association between hepatic iron deposition or serum iron values and hepatic fibrosis and inflammatory activity in patients with chronic hepatitis C virus infection. METHODS: In 100 consecutive patients with hepatitis C virus infection, tissue iron deposition was assessed by quantifying iron stain on liver biopsy specimens. Serum iron, ferritin, and transferrin saturation were determined by standard laboratory procedures. Statistical analyses incorporated potential confounders associated with hepatic fibrosis. RESULTS: Twenty-one patients had no fibrosis (stage 0), 13 had portal fibrosis (stage 1), 31 had periportal fibrosis (stage II), 10 had bridging fibrosis (stage III), and 25 had cirrhosis (stage IV). Positive iron stain found in liver biopsy specimens of 19 patients was associated with stage III or IV fibrosis (p = 0.004). No significant difference was found between the iron concentration or the hepatic iron index in patients with stage III or IV fibrosis compared with patients with stage I or II fibrosis. At least 1 of 3 serum iron values assessed was abnormal in 55 patients. In univariate analysis, elevated serum iron (p = 0.01), serum ferritin (p < 0.001), and transferrin saturation (p = 0.002) were associated with stage III or IV fibrosis. In multivariate analysis, the only independent predictive factor of severe hepatic fibrosis was serum ferritin (p < 0.02; odds ratio = 11.35). The serum ferritin value and tissue iron stain had a significant positive correlation (p < 0.001). CONCLUSIONS: Increased hepatic iron deposition may be associated with more advanced hepatic fibrosis in patients with chronic hepatitis C virus infection. The serum ferritin value, an independent predictor of severe hepatic fibrosis in patients with chronic hepatitis C virus infection, may predict hepatic iron deposition and severity of fibrosis.