Cytoprotection by activated protein C (aPC) after ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation, and hence, cell-death forms disjunct from immunologically silent apoptosis are, in theory, more likely to be relevant. Because pyroptosis (ie, cell death resulting from inflammasome activation) is typically observed in IRI, we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRIs. aPC treatment before or after myocardial IRI reduced infarct size and Nlrp3 inflammasome activation in mice. Kinetic in vivo analyses revealed that Nlrp3 inflammasome activation preceded myocardial injury and apoptosis, corroborating a pathogenic role of the Nlrp3 inflammasome. The constitutively active Nlrp3A350V mutation abolished the protective effect of aPC, demonstrating that Nlrp3 suppression is required for aPC-mediated protection from IRI. In vitro aPC inhibited inflammasome activation in macrophages, cardiomyocytes, and cardiac fibroblasts via proteinase-activated receptor 1 (PAR-1) and mammalian target of rapamycin complex 1 (mTORC1) signaling. Accordingly, inhibiting PAR-1 signaling, but not the anticoagulant properties of aPC, abolished the ability of aPC to restrict Nlrp3 inflammasome activity and tissue damage in myocardial IRI. Targeting biased PAR-1 signaling via parmodulin-2 restricted mTORC1 and Nlrp3 inflammasome activation and limited myocardial IRI as efficiently as aPC. The relevance of aPCmediated Nlrp3 inflammasome suppression after IRI was corroborated in renal IRI, where the tissue protective effect of aPC was likewise dependent on Nlrp3 inflammasome suppression. These studies reveal that aPC protects from IRI by restricting mTORC1- dependent inflammasome activation and thatmimicking biased aPC PAR-1 signaling using parmodulins may be a feasible therapeutic approach to combat IRI.

کاردیولیپین در واقع فسفولیپیدی است که در غشاء داخلی میتوکندری و غشاء پلاسمائی باکتریها وجود دارد.این ماده جزء اصلی آنتی ژنیک آنتی ژن های واسرمن است که در آزمون سرولوژیک غیر ترپونمایی سیفیلیس به کار میرود. از نظر بالینی مهمترین اندیکاسیون اندازه گیری آنتی کاردیولیپین در مبتلایان به لوپوس با سابقه ترومبوز است. و روش اندازه گیری آن الایزا می باشد. و بر روی سرم انجام میشود.

Real-time quantitative PCR (qPCR) assay of sputum or nasopharyngeal specimens has shown promising results in the detection of pneumococcal community-acquired pneumonia (PncCAP). We applied qPCR for the autolysin gene (lytA) and compared sputum and nasopharyngeal swab (NPS) pneumococcal loads in elderly patients with community-acquired pneumonia (CAP), and specifically in patients with PncCAP, to those in patient groups with other respiratory diseases. We studied patients aged 65 years with radiologically confirmed CAP, clinical CAP not retrospectively radiologically confirmed, other acute respiratory infections, or stable chronic lung disease. Pneumococcal etiology of CAP was ascertained by using a combination of multiple diagnostic methods. We analyzed sputum and NPS specimens by lytA qPCR with 104 pneumococcal genome equivalents (GE)/ml as a cutoff for positivity. Among PncCAP patients, lytA qPCR detected pneumococci in 94% of the sputum samples and in large quantities (mean, 6.82 1.02 log10 GE/ml) but less frequently in NPS (44%) and in smaller quantities (5.55 0.92 log10 GE/ml). In all other patient groups, 10% of the sputum samples and 5% of the NPS samples were lytA qPCR positive; but when they were positive, the sputum pneumococcal loads were similar to those in the PncCAP patients, suggesting a pneumococcal etiology in these patients. This was supported by other pneumococcal assay results. Overall, sputum lytA qPCR positivity was more common in PncCAP patients than in the other patient groups, but the quantitative results were mainly similar. NPS lytA qPCR was less sensitive than sputum lytA qPCR in detecting PncCAP.

این آزمایش جهت تشخیص و پیگیری بیماری هپاتیت B که به وسیلۀ ویروس هپاتیت ایجاد می‌شود، بررسی آنتی‌بادی‌های ساخته شده توسط بدن (HBs Ab) که می‌توانند هم از طریق تحریک به وسیلۀ واکسن هپاتیت تولید شده باشند و هم می‌توانند به علت ابتلا به بیماری هپاتیت به وجود آمده باشند.

Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studies have shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. In this study, the expression of fibulin-5 in colorectal cancer (CRC) and its clinical significance were assessed.

سندروم رت؛ کابوسی برای والدین! نوزاد متولد شده ظاهرا سالم است اما پس از ۱ سالگی، تکامل و رشد او متوقف می‌شود. مهارت‌های گفتاری و حرکتی او مختل می‌شود. تنفس نامنظم، تشنج و دیگر مشکلات، از جمله علائم این اختلال هستند. سندروم رت نوعی بیماری ژنتیکی-نورولوژیکی است و اغلب دختران را درگیر می‌کند. اکثر بیماران مبتلا به سندروم رت با مراقبت‌های تمام وقت و خاص، می‌توانند تا میان‌سالی زنده بمانند.

There is substantial evidence that stool culture and parasitological examinations are of minimal to no value after 3 days of hospitalization. We implemented and studied the impact of a clinical decision support tool (CDST) to decrease the number of unnecessary stool cultures (STCUL), ova/parasite (O&P) examinations, and Giardia/Cryptosporidium enzyme immunoassay screens (GC-EIA) performed for patients hospitalized 3 days. We studied the frequency of stool studies ordered before or on day 3 and after day 3 of hospitalization (i.e., categorical orders/total number of orders) before and after this intervention and denoted the numbers and types of microorganisms detected within those time frames. This intervention, which corresponded to a custom-programmed hard-stop alert tool in the Epic hospital information system, allowed providers to override the intervention by calling the laboratory, if testing was deemed medically necessary. Comparative statistics were employed to determine significance, and cost savings were estimated based on our internal costs. Before the intervention, 129/670 (19.25%) O&P examinations, 47/204 (23.04%) GC-EIA, and 249/1,229 (20.26%) STCUL were ordered after 3 days of hospitalization. After the intervention, 46/521 (8.83%) O&P examinations, 27/157 (17.20%) GC-EIA, and 106/1,028 (10.31%) STCUL were ordered after 3 days of hospitalization. The proportions of reductions in the number of tests performed after 3 days and the associated P values were 54.1% for O&P examinations (P 0.0001), 22.58% for GC-EIA (P  0.2807), and 49.1% for STCUL (P 0.0001). This was estimated to have resulted in $8,108.84 of cost savings. The electronic CDST resulted in a substantial reduction in the number of evaluations of stool cultures and the number of parasitological examinations for patients hospitalized for more than 3 days and in a cost savings while retaining the ability of the clinician to obtain these tests if clinically indicated.

غده ای پروانه ای شکل می‌باشد که در قسمت بالایی حنجره، در جلوی گلو قرار دارد. این غده با ترشح هورمون تیروکسین (T4)، تری‌یدو‌تیروئین (T3)و کلسی‌تونین در تنظیم سوخت وساز بدن نقش دارد. هورمون محرک تیروئید(TSH) که از هیپوفیز ترشح می شود بر عملکرد این غده تاثیر می گذارد. هرگونه اختلال در عملکرد این غده، مکانیسم سوخت وساز را در تمامی بخش‌های بدن تحت تاثیر قرار می‌دهد.

Similar to mecA, mecC confers resistance against beta-lactams, leading to the phenotype of methicillin-resistant Staphylococcus aureus (MRSA). However, mecC-harboring MRSA strains pose special difficulties in their detection. The aim of this study was to assess and compare different phenotypic systems for screening, identification, and susceptibility testing of mecC-positive MRSA isolates. A well-characterized collect('io of mecC-positive S. aureus isolates (n 111) was used for evaluation. Routinely used approaches were studied to determine their suitability to correctly identify mecC-harboring MRSA, including three (semi)automated antimicrobial susceptibility testing (AST) systems and five selective chromogenic agar plates. Additionally, a cefoxitin disk diffusion test and an oxacillin broth microdilution assay were examined. All mecC-harboring MRSA isolates were able to grow on all chromogenic MRSA screening plates tested. Detection of these isolates in AST systems based on cefoxitin and/or oxacillin testing yielded overall positive agreements with the mecC genotype of 97.3% (MicroScan WalkAway; Siemens), 91.9% (Vitek 2; bioMérieux), and 64.9% (Phoenix, BD). The phenotypic resistance pattern most frequently observed by AST devices was “cefoxitin resistance/oxacillin susceptibility,” ranging from 54.1% (Phoenix) and 83.8% (Vitek 2) to 92.8% (WalkAway). The cefoxitin disk diffusion and oxacillin broth microdilution assays categorized 100% and 61.3% of isolates to be MRSA, respectively. The chromogenic media tested confirmed their suitability to reliably screen for mecC-harboring MRSA. The AST systems showed false-negative results with varying numbers, misidentifying mecC-harboring MRSA as methicillin-susceptible S. aureus. This study underlines cefoxitin’s status as the superior surrogate mecC-positive MRSA marker.

نوروبلاستوما نوعی سرطان بوده که اغلب کودکان را تحت تاثیر قرار می دهد. نوروبلاستوما زمانی رخ می دهد که سلول های عصبی نابالغ به نام نوروبلاست ها غیرعادی شده و به صورت کنترل نشده تکثیر شوند و باعث ایجاد تومور گردند. عمدتاً، تومور از بافت های عصبی غدد آدرنال واقع در بالای هر کلیه منشأ می گیرد. سایر نقاط شایع برای شکل گیری تومور شامل بافت عصبی در شکم ، سینه ، گردن یا لگن می باشد. نوروبلاستوما می تواند به سایر نقاط بدن مثل استخوان ها ، کبد یا پوست انتشار یابد.

بشر از اول با معضلی به نام مسمومیت غذایی در گیر بوده و هر انسانی حد اقل یک‌بار در عمر خود به این عارضه مبتلا شده است و یکی از مهم‌ترین عوامل مسمومیت غذایی در انسان سموم باکتریایی ازجمله انتروتوکسینهای استافیلوکوک اورئوس می‌باشد.

Activation of trypsin from proteolytic cleavage of trypsinogen in the pancreas can lead to acute pancreatitis. Calcitonin gene related peptide (CGRP) from both peripheral and central neurons is involved in a variety of physiological/pathophysiological processes, especially sensory (nociceptive) and efferent (effector) functions. To better understand the change of trypsin/CGRP in acute pancreatitis, the study investigated the serum level of trypsin/CGRP in patients with acute pancreatitis.

مهارت های آزمایشگاهی در خون شناسی -دکتر حبیب اله گل افشان عضو هیات علمی دانشگاه علوم پزشکی شیراز

Clostridium sordellii is an often-lethal bacterium causing human and animal disease. Crucial to the infectious cycle of C. sordellii is its ability to produce spores, which can germinate into toxin-producing vegetative bacteria under favorable conditions. However, structural details of the C. sordellii spore are lacking. Here, we used a range of electron microscopy techniques together with superresolution optical microscopy to characterize the C. sordellii spore morphology with an emphasis on the exosporium. The C. sordellii spore is made up of multiple layers with the exosporium presenting as a smooth balloon-like structure that is open at the spore poles. Focusing on the outer spore layers, we compared the morphologies of C. sordellii spores derived from different strains and determined that there is some variation between the spores, most notably with spores of some strains having tubular appendages. Since Clostridium difficile is a close relative of C. sordellii, their spores were compared by electron microscopy and their exosporia were found to be distinctly different from each other. This study therefore provides new structural details of the C. sordellii spore and offers insights into the physical structure of the exosporium across clostridial species.

خون ما از بالغ بر میلیاردها سلول ساخته شده است، از این بین گلبول های قرمز خون دارای هموگلوبین هستند. هموگلوبین پروتئینی حاوی آهن است که مسئول حمل اکسیژن به سراسر بدن می باشد. فرم های مختلفی از هموگلوبین وجود دارند که می توانند در خون یافت شوند.

لنفوسیتها در بیماريهاي ویروسی دچار تغییرات چشمگیر در سیتوپلاسم و هسته می گردند . این تغییرات خوشخیم در آزمایشگاههاي مختلف به صورتهاي زیر گزارش میشود:

Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA.

شاید تصور می‌کنید باکتری‌های فلور موجود در بدن بدون فعالیت خاصی تنها در جای خود نشسته‌اند و منتظرند قسمتی از مواد غذایی مصرف‌شده به روده وارد شود؛ اما پژوهش‌های جدید نشان می‌دهند گفتگوهای مداومی بین این باکتری‌ها و کدهای ژنتیکی بدن در جریان است. موادی که توسط باکتری‌های مفید موجود در سیستم گوارشی تولید می‌شوند، تأثیر عجیبی بر کروموزومِ سلول‌های مجاورش دارد. این اکتشاف مسیری برای جلوگیری از سرطان‌های گوارشی خطرناک پیشنهاد می‌کند.

Although autoantibodies have been used for decades as diagnostic and prognostic markers in type 1 diabetes (T1D), further analysis of developmental abnormalities in B cells could reveal tolerance checkpoint defects that could improve individualized therapy. To evaluate B cell developmental progression in T1D, immunophenotyping was used to classify circulating B cells into transitional, mature naïve, mature activated, and resting memory subsets. Then each subset was analyzed for the expression of additional maturation-associated markers. While the frequencies of B cell subsets did not differ significantly between patients and controls, some T1D subjects exhibited reduced proportions of B cells that expressed transmembrane activator and CAML interactor (TACI) and Fas receptor (FasR). Furthermore, some T1D subjects had B cell subsets with lower frequencies of class switching. These results suggest circulating B cells exhibit variable maturation phenotypes in T1D. These phenotypic variations may correlate with differences in B cell selection in individual T1D patients.

بزرگترين غده بدن است و بعد از پوست بزرگترين عضو بدن است كه در زير پرده ديافراگم قرار گرفته است كبد در بسياري از اعمال متابوليكي بدن از جمله پروتئين سازي و سم زدايي شركت دارد . از ديگر اعمال سلولهاي كبدي ذخيره سازي مواد مختلفي از جمله تري گليسريد ، گليكوژن و ويتامينها مي باشد ، اعمال متابوليكي سلولهاي كبدي كه مهمترين آن گلوكونئوژنز يا تبديل چربيها و اسيد هاي آمينه به گلوكز و دآميناسيون اسيدهاي آمينه براي توليد اوره است .