Management of ST-segment-elevation myocardial infarction during the coronavirus disease 2019 (COVID-19) outbreak: Iranian“247” National Committee's position paper on primary percutaneous coronary intervention

World Health Organization has designated coronavirus disease 2019 (COVID-19) as a pandemic. During the past several weeks, a considerable burden has been imposed on the Iranian's healthcare system. The present document reviewed the latest evidence and expert opinion regarding the management of ST-segment-elevation myocardial infarction during the outbreak of COVID-19 and outlines a practical algorithm for it.     

Outcome of lupus nephritis in Iranian children: prognostic significance of certain features

The objective of this study was to determine the clinical and histopathological features and outcome of children with lupus nephritis (LN). Of 84 children with systemic lupus erythematosus (SLE), we retrospectively studied 58 children (69%) under 15 years of age with biopsy-proven LN who had been followed between October 1989 and January 2005. The mean age at diagnosis or initial referral was 10.6 ± 2.25 years, and the mean follow-up was 5.3 ± 4.1 years. Class IV LN was observed in 34 (58.6%) patients. The 5-year patient and renal survival rates were 82.5 and 78.5%, respectively, in the total group, and 75 and 85.8%, respectively, in patients with Class IV LN. No independent predictor of unfavorable outcome, including renal histology, was detected by multivariate analysis. The mid-term patient and the renal survival rates of Iranian children with biopsy-proven LN are high. Within 5 years of follow-up, renal histology was not a predictor for survival.     

Molecular typing of Epidermophyton floccosum isolated from patients with dermatophytosis by RAPD-PCR

We evaluated the ability of randomly amplified polymorphic DNA (RAPD) to type Epidermophyton floccosum isolates recovered from patients with dermatophytosis originating from different regions of Iran. A total of 13 clinical isolates of E. floccosum obtained from Iranian patients were analyzed by RAPD with 7 arbitrary primers (OPN16, OPD18' OPU15, OPX19, R28, OPA04 and OPAA17). Among the applied primers, OPN16 produced banding patterns from all the isolates. In addition, some of the isolates had very close relation. The phenon line which represented the mean similarities was at the value of 73%. At this level, 4 groups were characterized. Two isolates of a patient had different molecular patterns, suggesting infection transmission from different sources in the case of a single patient. RAPD-PCR provided a rapid and practical tool for identification of E. floccosum isolates, which was independent of morphological characteristics, and enhanced laboratory diagnosis of dermatophytosis.     

Effect of ultrasound on enzymatic activity of selected plasminogen activators

INTRODUCTION: Ultrasound has been shown to accelerate enzymatic fibrinolysis with adjunctive plasminogen activators. Additionally, ultrasound is known for interaction with biological substances on molecular level in sonodynamic therapy and sonochemistry. Therefore, we investigated the possibility of ultrasound affecting the biological activity of plasminogen activators used in thrombolysis treatment. MATERIALS AND METHODS: Four currently marketed plasminogen activators were evaluated: urokinase, streptokinase, alteplase, and reteplase. The tests were conducted in reconstituted, undiluted plasminogen activator. Each test contained a control and a test sample. The test sample was incubated in a water bath at temperatures of approximately 34 degrees C and exposed to ultrasound for 1h. The control was incubated in the same water bath as the test sample for the same duration but was not exposed to ultrasound. The ultrasound frequency and intensity used for this experiment were 1 MHz and 2.5-3.1W/cm2, respectively. For quantitative measurement of biological activity of the test and control samples of each plasminogen activator either specific chromogenic substrates or the fibrin clot liquefaction time was used. RESULTS: Student t-test was applied to compare treated vs. control group for each plasminogen activator. The p-value for urokinase, streptokinase, alteplase, and reteplase are 0.43, 0.76, 0.70, and 0.30, respectively. CONCLUSION: Ultrasound with a frequency of 1 MHz and intensities of 2.5-3.1W/cm2 had no statistically significant impact on biological activity of selected plasminogen activators.     

Caregivers' knowledge with burned children and related factors towards burn first aid: A systematic review

This systematic review aimed to examine the caregivers' knowledge with burned children and related factors towards burn first aid. A comprehensive, systematic search was performed in different international electronic databases, such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database using keywords extracted from Medical Subject Headings such as “Knowledge”, “First aid”, “Caregiver”, “Burn”, and “Child” from the earliest to the December 1, 2022. The quality of the studies included in this systematic review was evaluated by using the appraisal tool for cross-sectional studies (AXIS tool). A total of 11 763 caregivers of children with burns were enrolled in 14 studies. Of the participants, 78.81% were female and 41.15% had a university education. The mean score of caregivers' knowledge with burned children towards burn first aid was 51.44 out of 100. The knowledge of caregivers of burned children towards burn first aid had a significant positive relationship with the level of education, first aid training, age of caregivers, history of burn, number of children, monthly income, social status, and attitude. In addition, caregivers' knowledge had a significant negative relationship with the number of children. Furthermore, there was a significant relationship between caregivers' knowledge and level of education, monthly income, smoking, and previous knowledge of first aid. The level of caregivers' knowledge with burned children towards burn first aid was moderate. Therefore, health managers and policymakers can improve the knowledge of caregivers of burned children towards burn first aid by creating suitable platforms for face-to-face training as well as online training using websites.     

Association of small foci of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) with adenocarcinoma of the lung

DIPNECH is regarded as a precursor lesion of neuroendocrine lung tumors, specifically carcinoids. A relationship with lung adenocarcinomas has not been clearly established so far. We present a series of four cases with a concomitant presence of adenocarcinoma and DIPNECH in the lung.     

Complete Nucleotide Sequence of KPC-3-Encoding Plasmid pKpQIL in the Epidemic Klebsiella pneumoniae Sequence Type 258

We have determined the entire DNA sequence of plasmid pKpQIL, the bla_KPC-3-carrying plasmid harbored by the carbapenem-resistant Klebsiella pneumoniae clone sequence type 258 (ST 258) in Israel. pKpQIL is a 113,637-bp, self-transmissible plasmid that belongs to the incompatibility group IncFII. It consists of a large backbone of a pKPN4-like plasmid and carries the bla_KPC-3-containing Tn4401a transposon of a pNYC-like plasmid.Bacterial plasmids are extrachromosomal genetic elements that play a crucial role in the acquisition and dissemination of antibiotic resistance determinants through inter- and intraspecies horizontal gene transfer. Resistance to carbapenems in Enterobacteriaceae does not occur naturally but rather arises by the acquisition of various β-lactamases encoded by transferrable plasmids (15).During the last decade, carbapenem-resistant KPC-producing Enterobacteriaceae strains, particularly Klebsiella pneumoniae, have emerged and spread globally (14). These KPC-producing strains harbor plasmids encoding KPC-type carbapenemases. Several KPC-encoding plasmids from K. pneumoniae were partially or fully sequenced, including bla_KPC-2- and bla_KPC-3-carrying plasmids from the United States (6) and bla_KPC-2-carrying plasmids from Greece, Colombia (12), and China (19). These plasmids differed in size and harbored the transposon Tn4401, proven to be involved with the dissemination of bla_KPC (12, 14). This element has been found entirely or in part in all of the bla_KPC-encoding plasmid sequences to date and has been found in one of two isoforms, a or b, that differ by a 100-bp deletion upstream of the bla_KPC gene (6). A variant of this transposon, harboring ISKpn8, was reported from China (19).In 2006, an extremely drug-resistant KPC-3-producing K. pneumoniae strain emerged in Israel (8), causing a nationwide clonal outbreak. This strain is genetically related to K. pneumoniae outbreak isolates from various regions in the United States (13), identified as sequence type 258 (ST 258) (7). Soon thereafter, this sequence type was found to have spread further geographically to China and several countries within the Middle East, Europe, and South America (1, 4, 11, 20). The K. pneumoniae ST 258 strain isolated in Israel is susceptible only to gentamicin and colistin (8), thereby limiting therapeutic options and thus posing a clinical and public health threat (18). Clinical isolates of K. pneumoniae ST 258 studied during the last 4 years in Israel have been found to harbor an identical bla_KPC-3-encoding plasmid of about 105 kb (13), designated pKpQIL (9). This plasmid was shown to be self-conjugative and exclusively responsible for carbapenem resistance in these isolates. pKpQIL contains the Tn4401 element and TEM-1 gene (9). In this paper, we report the complete sequence and analysis of pKpQIL.Plasmid pKpQIL was purified from a representative clinical isolate of carbapenem-resistant KPC-3-producing K. pneumoniae ST 258, isolate 557. This isolate harbored two plasmids: pKpQIL and an additional 240-kb plasmid (9). Plasmid DNA was purified using a NucleoBond PC 100 plasmid midi kit (Macherey-Nagel GmbH, Düren, Germany) and transformed into Escherichia coli GeneHogs (Invitrogen Corp., Dorset, United Kingdom). Transformants harboring the bla_KPC gene were identified by PCR and selected as described previously (8). pKpQIL was isolated and subjected to a complete DNA sequence analysis using “454 massively parallel DNA sequencing” (Dyn G. S. Ltd., Caesarea, Israel). The resulting sequences were assembled to eight contigs using the 454 Newbler assembler software (10). Sequence gaps on the plasmid were closed by PCR and sequencing. GeneMark (http://exon.biology.gatech.edu/gmhmm2_prok.cgi) was used to predict the putative open reading frames (ORFs). Overlapping and closely clustered ORFs were manually inspected. The G+C content of the plasmid was identified using the GC calculator (http://www.sciencebuddies.org/science-fair-projects/project_ideas/Genom_GC_Calculator.shtml). The nucleotide acid and deduced protein sequences were analyzed at the NCBI website (http://www.ncbi.nlm.nih.gov/).The entire DNA sequence of pKpQIL is composed of 113,637 bp forming a circular plasmid (Fig. ​(Fig.1)1) with a G+C content of 53.9%. One hundred thirty-six open reading frames were identified. The products of 67 ORFs showed a high similarity to proteins of known functions. Sequence analysis of pKpQIL showed a high similarity with two K. pneumoniae plasmids. Seventy-five percent of the sequence was highly similar to that of plasmid pKPN4 (GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"CP000649","term_id":"150958389","term_text":"CP000649"}}CP000649), and 12% of pKpQIL was highly similar to the partially sequenced plasmid pNYC (GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"EU176011","term_id":"167077380","term_text":"EU176011"}}EU176011).Open in a separate windowFIG. 1.Genetic map of the full-length, 113-kb pKpQIL plasmid. The arrows indicate gene location and orientation. Predicted ORFs with known functions are indicated by black arrows. ORFs of hypothetical proteins are indicated by white arrows. Boundaries of Tn4401 are marked with a bracket. The plasmid map was drawn using Redasoft visual cloning software. The black arc inside the circle shows the region in common with plasmid pKPN4 of K. pneumoniae MGH 78578, and the gray arc indicates the region in common with plasmid pNYC of K. pneumoniae strain YC.The region in common between pKpQIL and pKPN4 consists of 86,610 bp (positions 26360 to 112970 on pKpQIL). This region shows 99% identity with plasmid pKPN4 at both the sequence and the gene organization level. This plasmid is one of five plasmids harbored by multidrug-resistant K. pneumoniae MGH 78578 (ATCC 700721) that was isolated from the sputum of a 66-year-old male pneumonia patient hospitalized in Massachusetts General Hospital in 1994 (http://www.expasy.ch/sprot/hamap/KLEP7.html). The common coding region of these two plasmids consists of genes responsible for plasmid maintenance, transmission, and antibiotic resistance (Fig. ​(Fig.11).The genes identified on pKpQIL that are responsible for plasmid maintenance and stability, as in other enteric plasmids (2), include plasmid segregation genes (parA and parB), type I restriction modification systems, and mediators of plasmid stability (stbA and stbB). The tra gene region, involved in plasmid transfer via conjugation, makes up approximately 35 kb (30% of the plasmid length) of both plasmids, supporting our previous findings that pKpQIL is self-transmissible (9). An additional common region between pKpQIL and pKPN4 carries antibiotic resistance genes, including the aadA gene, bla_OXA-9, and bla_TEM-1 and is similarly positioned in the transposon Tn1331, as reported previously (17). Sequence analysis of this region showed two main modifications. The first is the truncation of aadA being a result of the IS26 insertion at position 682 of the aadA gene. A second is a nonsense mutation (A→G) at position 350 of the bla_OXA-9 gene, leading to inactivation of this gene. The presence of bla_OXA-9 and bla_TEM-1 together with bla_KPC-3 was previously reported in other K. pneumoniae isolates (5, 16, 21).From positions 4829 to 18898 (14,070 bp), pKpQIL shows 99% identity with the plasmid pNYC of the K. pneumoniae strain YC (12). This region contains the 10-kb bla_KPC-3-carrying Tn4401 transposon responsible for carbapenem resistance that has been previously characterized (6, 12). The Tn4401 transposon of pKpQIL has a 100-bp deletion and is therefore isoform a, as in agreement with previous findings (7).The remaining part of pKpQIL (overall, 12,954 bp) includes 4,828 bp upstream of Tn4401 and 8,126 bp downstream of Tn4401. The 4,828 bp show a 94% homology to the plasmid pKP91 of K. pneumoniae 342 (GenBank accession number {"type":"entrez-nucleotide","attrs":{"text":"NC_011281","term_id":"206575367","term_text":"NC_011281"}}NC_011281). This region includes four hypothetical proteins, an endonuclease, and the origin of replication of pKpQIL-RepA and -RepA2 (Fig. ​(Fig.1).1). RepAs of pKpQIL show 96 to 97% homology to RepAs of pKP91. The 8,126-bp region, located downstream of Tn4401, encodes for two transposases, a hypothetical protein, a putative resolvase, and IS26 (Fig. ​(Fig.11).pKpQIL was found to belong to the IncFII-like incompatibility group, based on the RepA sequence (3). RepA showed 89% amino acid identity with the IncFII RepA from Salmonella enterica plasmid pSLT (GenBank accession number {"type":"entrez-nucleotide","attrs":{"text":"AE006471","term_id":"973795114","term_text":"AE006471"}}AE006471). Previously reported IncFII plasmids were also identified to carry antibiotic resistance genes, including CTX-M- and SHV-type extended-spectrum β-lactamase (ESBL)-encoding genes, plasmid-mediated quinolone resistance genes, or ampC genes (2). pKpQIL is the first bla_KPC-carrying plasmid found to belong to the IncFII group. PCR-based replicon typing (PBRT) applied by Carattoli et al. to select bla_KPC-2-carrying plasmids from different outbreak strains resulted in negative results for all the replicons (2). Other bla_KPC--carrying plasmids analyzed in the same study belonged to other replicon types, such as plasmid 9 of K. pneumoniae from the United States (GenBank accession number {"type":"entrez-nucleotide","attrs":{"text":"FJ223607","term_id":"209574213","term_text":"FJ223607"}}FJ223607), found to belong to the IncN-like type (2), and plasmid pBC633 of K. pneumoniae strain KN633 from Colombia (GenBank accession number {"type":"entrez-nucleotide","attrs":{"text":"EU176012","term_id":"167077390","term_text":"EU176012"}}EU176012), which had a ColE-like replication origin (2).pKpQIL was found to carry two replicons. In addition to the IncFII-like replicon mentioned previously, another origin of replication (RepA, position 53179 to 54075) exists on the common part of pKpQIL and pKPN4 and shows 100% homology to RepA of pKPN4. These findings correlate to other known IncF plasmids that often carry more than one replicon and are known as the low-copy-number plasmids described by Carattoli et al. (2). The IncF-like plasmids are known to be limited in their host range to the genera of Enterobacteriaceae (2).The KPC-encoding plasmids from K. pneumoniae that have been fully sequenced are plasmid 9 (GenBank accession number {"type":"entrez-nucleotide","attrs":{"text":"FJ223607","term_id":"209574213","term_text":"FJ223607"}}FJ223607), plasmid 12 (GenBank accession number {"type":"entrez-nucleotide","attrs":{"text":"FJ223605","term_id":"209574095","term_text":"FJ223605"}}FJ223605), and plasmid 15S (GenBank accession number {"type":"entrez-nucleotide","attrs":{"text":"FJ223606","term_id":"209574188","term_text":"FJ223606"}}FJ223606). Other than the common Tn4401 region, necessary for the spread of the bla_KPC gene (14), these KPC-encoding plasmids are different in their gene organization and in their antibiotic resistance features. The majority of these plasmids (pKP048 from China [19], pNGR from Greece, and pNYC from the United States [12]) were demonstrated to be self-conjugative, as was pKpQIL (9), while others, such as pBC633 (GenBank accession number {"type":"entrez-nucleotide","attrs":{"text":"EU176012","term_id":"167077390","term_text":"EU176012"}}EU176012), were not (12).Previous findings indicate that all bla_KPC-carrying plasmids investigated harbor the Tn4401 structure that is located on different plasmid backbones. The complete sequencing of pKpQIL presented in the current study suggests that it was formed as a result of the plasmid rearrangement of a pKPN4-like and pNYC-like plasmid. Additional studies on KPC-encoding plasmids harbored by K. pneumoniae ST 258 from other geographical areas and plasmid comparison studies are warranted in order to reveal the mechanisms driving the success of certain KPC-carrying plasmids compared to others.