Errors in diagnosis of infective endocarditis.

Infective endocarditis (IE) is now the third or fourth most common life-threatening infectious disease. The high morbidity and mortality rates in the absence of appropriate care necessitate a thorough understanding of the obstacles towards the early diagnosis and management of IE. The aim of this study was to evaluate the frequency of discrepancy in diagnosis (i.e. discrepancy between the reason for admission and discharge diagnosis) and associated factors in patients with IE. It was a retrospective review of hospital records of all adult patients admitted in a 1000-bed academic general hospital in Mashhad, Iran with the discharge diagnosis of IE. Discrepancy in diagnosis on admission was observed in 64 (54.2%) of 118 episodes of IE. For patients with discrepant diagnosis, the odds of poor outcome were more than two times higher than the odds of those with the non-discrepant diagnosis. Multivariate analysis identified the only history of prosthetic valve replacement as an independent factor in predicting non-discrepant diagnosis. We suggest that in facing a patient with the complex clinical scenario, proposing a comprehensive clinical syndrome that includes predisposing factors instead of a symptom or finding-based diagnosis can help making the differential diagnosis more accurate.

Nosocomial outbreak of Crimean-Congo haemorrhagic fever.

We report a nosocomial outbreak of Crimean-Congo haemorrhagic fever (CCHF) that affected six patients in June 2009 in Ghaem Hospital, Mashhad, Iran, apparently related to one index case. The last four cases were healthcare workers. Infection was spread by percutaneous exposure to two cases, and probably by direct contact with blood, clothes and sheets, to three others. The diagnosis in the two fatal cases was not confirmed virologically. The diagnosis in four cases who survived was confirmed by specific reverse transcription polymerase chain reaction. The patients were treated with ribavirin. In endemic areas, every patient presenting with a febrile haemorrhagic syndrome should be considered to have a viral haemorrhagic fever until proven otherwise. Patients who meet the criteria for probable CCHF should be admitted to hospital and treated with ribavirin. Appropriate isolation precautions should be immediately initiated.

Highly selective MXene/V2O5/CuWO4-based ultra-sensitive room temperature ammonia sensor.

A Schottky junction based on Ti3C2Tx MXene sheet integrated with marigold flower-like V2O5/CuWO4 heterojunction was designed and fabricated for robust ammonia sensing by monitoring the electrical resistance changes in air and ammonia. The electron transport behavior of the sensor was investigated by electrochemical analysis, ultraviolet photoelectron spectroscopy and reflection electron energy loss spectroscopy. Besides, negative zeta potential obtained for sensor components was in consistent with surface functional groups (e.g. OH and F) observed by XPS analysis helping better understanding of the ammonia sensing mechanism. The results desirably confirmed high sensitivity, selectivity, linear range (1-160 ppm), the limit of quantification, repeatability, long-term stability, very short response time (few seconds) and low working temperature (25 °C) of the sensor. The measurements on the resistance changes of the MXene/V2O5/CuWO4-based sensor under the exposure to various types of analytes (Ammonia, Acetone, Benzene, Chloroform, DMF, Ethanol, humidity (80%), Methanol and Toluene as well as NO, NO2, H2S, SO2, CO and CH4) at different concentrations revealed that the fabricated sensor is excellently selective to ammonia with ultra-high sensitivity. Intra-day stability (7 runs a day) and long-term stability (every 10 days over 70 days) as important sensor characteristics were investigated at 51 ppm and ambient temperature, which showed very good repeatability and recoverability in both short and long periods for sensing the ammonia. Overall, MXene/V2O5/CuWO4 was shown to be cost-effective, easy to handle and suitably applicable for simple, ultrafast and extremely efficient trace ammonia detection, which could be of high interest for future exhaled breath analysis and the development of a novel noninvasive diagnostic strategy to monitor chronic kidney disease to stop a large measure of unnecessary invasive testing.

Mutants of bovine pancreatic trypsin inhibitor lacking cysteines 14 and 38 can fold properly.

It is a generally accepted principle of biology that a protein's primary sequence is the main determinant of its tertiary structure. However, the mechanism by which a protein proceeds from an unfolded, disordered state to a folded, relatively well-ordered, native conformation is obscure. Studies have been initiated to examine the "genetics" of protein folding, with mutants of bovine pancreatic trypsin inhibitor (BPTI) being used to explore the nature of the specific intramolecular interactions that direct this process. Previous work with BPTI chemically modified at cysteines 14 and 38 indicated that transient disulfide bond formation by these residues contributed to efficient folding at 25 degrees C. In the present work, mutants of BPTI in which these cysteines were replaced by alanines or threonines were made and the mutant proteins were produced by a heterologous Escherichia coli expression system. At 25 degrees C in vitro, the refolding behavior of these mutants was characterized by a pronounced lag. However, when expressed at 37 degrees C in E. coli, or when refolded at 37 degrees or 52 degrees C in vitro, the mutant proteins folded readily into the native conformation, albeit at a rate somewhat slower than that exhibited by wild-type BPTI. These results indicate that, at physiological temperatures, BPTI lacking cysteines 14 and 38 can refold quantitatively.

HIV type 1 subtype A epidemic in injecting drug user (IDU) communities in Iran.

HIV-1 C2-V3 subgenomic regions of the env gene from Iranian seropositive injecting drug users (IDUs) living in Mashhad have been analyzed to evaluate molecular and phylogenetic relationships with IDUs living in Tehran and identify possible common founder virus isolates. The results show that the viral sequences of the Iranian IDUs are strongly related and form a single cluster within the A subtype related to African Ugandan/Kenyan sub-Saharan isolates. Pairwise nucleotide alignment shows higher average divergence values within the Mashhad group than the Tehran group. Furthermore, the Mashhad sequences show much less conserved amino acid residues in the V3 loop than the Tehran sequences. These data represent the first macro-analysis of the HIV-1 molecular evolution in the Iran and Middle East epidemics and may be extremely relevant to guide the development and implementation of diagnostic as well as preventive/therapeutic approaches in this region.

Herpes Simplex Encephalitis (HSE) and its outcome in the Patients who were Admitted to a Tertiary Care Hospital in Mashhad, Iran, over a 10-year Period.

INTRODUCTION: The effective cure rate of acyclovir emphasizes the importance of an early diagnosis and treatment in reducing the considerable mortality and the morbidity in patients with Herpes Simplex Encephalitis (HSE). METHODS: The demographic as well as clinical features, the lab data and the neuroimaging findings of the patients with HSE, which were confirmed by Cerebrospinal Fluid (CSF) PCR and/or brain MRI, were reviewed and analyzed statistically over a 10-year period. RESULTS: Over a 10-year period, the characteristics of 45 patients with HSE were reviewed. 34 (76%) out of the 45 patients showed positive CSF HSV-1 PCR results. 8 (18%) had a normal CSF analysis and a CSF/blood glucose ratio of less than 0.5 was observed in 13 (29%) patients, while 14% had PMN-dominant pleocytosis. 68% of the patients for whom brain MRI was performed, had temporal lobe involvement. While 37 (83%) patients recovered completely, 6 (13%) survived with sequelae, and 2 (4%) died. CONCLUSION: Because of the increasing number of atypical forms of HSE and the great impact of an early diagnosis and treatment on a favourable outcome, the acyclovir therapy should be administrated for any type of febrile encephalopathy of unknown aetiology, until HSE can be excluded.

Comparison of the cytotoxic effects of Juniperus sabina and Zataria multiflora extracts with Taxus baccata extract and Cisplatin on normal and cancer cell lines.

Isolation and identification of some potent anti-tumor compounds from medicinal plants has motivated researchers to screen different parts of plant species for the determination of anti-tumor effects. In this study, cytotoxic effects and IC(50) of specific concentrations of hydro-alcoholic extracts of fruits of Juniperus sabina and leaves of Zataria multiflora were compared with hydro-alcoholic extract of bark of Taxus baccata and Cisplatin, well-known anticancer compounds, on normal (CHO and rat fibroblast) and cancer (HepG2 and SKOV3) cell lines. The hydro-alcoholic extracts of the plants were prepared by percolation. The cytotoxic effects and IC(50) of the extracts on the cell lines were studied followed by colonogenic assay after 72 h incubation. The results showed that the extract of Juniperus sabina possesses lower IC(50) in comparison with Zataria multiflora extract on all 4 normal and cancer cell lines (P<0.05); but, IC(50) of the Juniperus sabina extract was significantly higher than the Taxus baccata extract and Cisplatin on all 4 normal and cancer cell lines (P<0.05). As a result, it is concluded that the extract of J. sabina has almost similar cytotoxicity with the extract of Taxus baccata on cancer cells.

Molecular and phylogenetic analysis of HIV-1 variants circulating among injecting drug users in Mashhad-Iran.

Genetic and phylogenetic information on the HIV-1 epidemic in Middle-East Countries, and in particular in Iran, are extremely limited. By March 2004, the Iranian Ministry of Health officially reported a cumulative number of 6'532 HIV positive individuals and 214 AIDS cases in the Iranian HIV-1 epidemic. The intra-venous drug users (IDUs) represent the group at highest risk for HIV-1 infection in Iran, accounting for almost 63% of all HIV-infected population. In this regards, a molecular phylogenetic study has been performed on a sentinel cohort of HIV-1 seropositive IDUs enrolled at the end of 2005 at the University of Mashhad, the largest city North East of Tehran. The study has been performed on both gag and env subgenomic regions amplified by Polymerase Chain Reaction (PCR) from peripheral blood mononuclear cells (PBMCs) and characterized by direct DNA sequence analysis. The results reported here show that the HIV-1 subtype A is circulating in this IDUs sentinel cohort. Moreover, the single phylogenetic cluster as well as the intra-group low nucleotide divergence is indicative of a recent outbreak. Unexpectedly, the Iranian samples appear to be phylogenetically derived from African Sub-Saharan subtype A viruses, raising stirring speculations on HIV-1 introduction into the IDUs epidemic in Mashhad. This sentinel study could represent the starting point for a wider molecular survey of the HIV-1 epidemics in Iran to evaluate in detail the distribution of genetic subtypes and possible natural drug-resistant variants, which are extremely helpful information to design diagnostic and therapeutic strategies.

An outbreak of food-borne group A Streptococcus (GAS) tonsillopharyngitis among residents of a dormitory.

Epidemics of food-borne pharyngitis due to group A Streptococcus are rarely reported. Here we present an outbreak of food-borne tonsillopharyngitis in female dormitories in the Islamic Republic of Iran. Throat swabs and cultures were performed on a number of patients, and of specimens from the nasopharynx and hands of staff who were involved in food processing. We planned a case-control study for assessing the source of epidemics. 11 out of 17 throat swabs of students were positive for Streptococcus group A and also 2 throat samples from asymptomatic cooks were positive. A DNA fingerprinting study showed that Streptococcus group A strains of 11 students and 1 cook had the same T agglutination pattern and M protein factor (M3/T13). It is suggested that group A streptococci as well as group C and G streptococci can cause epidemic food-borne pharyngitis. Regular health surveillance of food handlers and food preparation processes are important for prevention of such outbreaks.

Two-dimensional 1H NMR of three spin-labeled derivatives of bovine pancreatic trypsin inhibitor.

Three nitroxide spin-labeled monoderivatives of bovine pancreatic trypsin inhibitor were prepared with the amino-specific reagent succinimidyl 1-oxy-2,2,5,5-tetramethyl-3-pyrroline-3-carboxylate. The monoderivatives were purified by ion-exchange and affinity chromatography. Thin-layer maps of tryptic peptides of the monoderivatives showed that the spin-label was incorporated at either the alpha-amino group, Lys-15, or Lys-26. Two-dimensional J-correlated 1H NMR spectra of the monoderivatives were recorded. Spectra were also recorded after reduction by ascorbic acid of the nitroxide label to hydroxylamine. With the nitroxide label present, significant line-broadening effects on many of the cross peaks in the spectra were observed. The extent of line broadening for the C alpha H-NH cross peaks was qualitatively correlated with the distance between the labeled amino group and the average C alpha H-NH position in the crystal structure. The spin-label affects cross peaks of protons within approximately 15 A. This study suggests that it is feasible to accumulate sufficient intramolecular distances in order to determine protein solution structures with the aid of distance geometry algorithms.