The Role of ncRNAs in Covid-19 Pathogenesis

Genomic studies have shown that approximately 2% of the human genome encodes protein, and the rest consists of non-coding RNAs (ncRNA). ncRNAs are the modifications that can alter gene expression at different levels without making any changes on the DNA sequence. One of the most important function of non-coding RNAs is to modulate host immunity and inflammatory response by regulating chromatin structure and gene expression. The World Health Organization has declared Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as Coronavirus Disease 2019 (COVID-19). COVID-19 shows symptoms such as fever, cough, shortness of breath and it can lead to severe symptomatic acute respiratory distress syndrome (ARDS), bring along many problems such as cardiovascular complications, kidney damage, stroke and death. Virus host interactions associated with the immune system is also important beside the viral replication mechanism in the development of a successful therapeutic target for SARS-CoV-2. Epigenetic mechanisms that regulate virus-host interactions affect the extent and adequacy of immune and inflammatory responses that are important for clinical outcomes. Thus, identifying ncRNAs involved in SARS-CoV-2 infection will help to understand the epigenetic regulation underlying the immune response that occurs and to develop new specific strategies to prevent and treat the infection. In this review, the importance of ncRNA mediated gene regulation in SARS-CoV-2 infection and its role in the ongoing COVID-19 pandemic were discussed

Çan Linyiti ile Kayın Ağacı Odununun Sabit Yatakta Birlikte Yakılması

Bu çalışmada, linyit ve belirli oranlarda kayın ağacı odunu tozu karışımlarından hazırlanan 13 mm çaplı peletlerin ön ısıtmalı dikey bir fırın sisteminde doğal konveksiyonla yukarı yükselen hava içindeki yanma davranışları incelenmiştir. Karışımların tutuşma sürelerinin sıcaklık arttıkça kayın ağacının tutuşma süresine yaklaştığı ve uçucu madde yanma süresi boyunca iki yakıtın belirli ölçüde etkileştiği görülmüştür. Yakıtlar arasındaki bu etkileşimden dolayı uçucu madde yanma sürelerinin yanma hızları ile uyumlu olmadığı, ancak iki yakıtın ve karışımlarının karbon yanma sürelerinin genellikle yanma hızları ile uyumlu olduğu gözlendi. Uçucu madde ve karbon yanma hızındaki değişimin fırın başlangıç sıcaklığı ve karışım içerisindeki yakıt oranlarına bağlı olduğu görüldü

Medical Biology and Genetics Laboratory Book

80 Pages : İllustrations ; 26 cm

Pyrolysis kinetics of pine sawdust in a fixed bed

Currently worldwide studies are being done on the utilisation of lignocellulosic materials or biomasses as substitutes of fossil fuels to afford energy needs of today’s world. Pyrolysis is one of the most promising techniques for apprising biomass into economically viable renewable fuels. In this work, pyrolysis behaviour of pine sawdust was investigated experimentally in a fixed bed system with mass measurements under nitrogen as sweeping gas. The main objective was to interpret mass loss of pine sawdust during pyrolysis at varied heating rates and to estimate kinetic constants using the best mathematical model among the popular solid phase decomposition models. Regression tests are separately applied to conversion data for 473 – 593 K and 593 – 773 K temperature ranges, corresponding respectively decomposition of hemicelluloses and cellulose, and cellulose and lignin. The quality of fit increased with heating rate and none of the proposed models had any superiority to others. The results implied that volatiles evolution during pyrolysis was increasingly controlled chemically with heating rate

Tıbbi Biyoloji ve Genetik Laboratuvar Kılavuzu

Çevrimiçi (70 sayfa: şekil; 26 cm.

Comparison of conventional and CT-based planning for intracavitary brachytherapy for cervical cancer: target volume coverage and organs at risk doses

<p>Abstract</p> <p>Background</p> <p>To compare intracavitary brachytherapy (ICBT) planning methods for cervical cancer, based on either orthogonal radiographs (conventional plan) or CT sections (CT plan); the comparison focused on target volume coverage and dose volume analysis of organs at risk (OARs), by representing point doses defined by the International Commission on Radiation Units and Measurement (ICRU) and dose volume histograms (DVHs) from 3D planning.</p> <p>Methods</p> <p>We analyzed the dosimetric data for 62 conventional and CT-based ICBT plans. The gross tumor volume (GTV), clinical target volume (CTV) and organs at risk (OAR)s were contoured on the CT-plan. Point A and ICRU 38 rectal and bladder points were defined on reconstructed CT images.</p> <p>Results</p> <p>Patients were categorized on the basis of whether the >95% isodose line of the point-A prescription dose encompassed the CTV (group 1, n = 24) or not (group 2, n = 38). The mean GTV and CTV (8.1 cc and 20.6 cc) were smaller in group 1 than in group 2 (24.7 cc and 48.4 cc) (<it>P <</it>0.001). The mean percentage of GTV and CTV coverage with the 7 Gy isodose was 93.1% and 88.2% for all patients, and decreased with increasing tumor size and stage. The mean D2 and D5 rectum doses were 1.66 and 1.42 times higher than the corresponding ICRU point doses and the mean D2 and D5 bladder doses were 1.51 and 1.28 times higher. The differences between the ICRU dose and the D2 and D5 doses were significantly higher in group 2 than in group 1 for the bladder, but not for the rectum.</p> <p>Conclusion</p> <p>The CT-plan is superior to the conventional plan in target volume coverage and appropriate evaluation of OARs, as the conventional plan overestimates tumor doses and underestimates OAR doses.</p

Comparison of CT and integrated PET-CT based radiation therapy planning in patients with malignant pleural mesothelioma

<p>Abstract</p> <p>Background</p> <p>When combined with adequate tumoricidal doses, accurate target volume delineation remains to be the one of the most important predictive factors for radiotherapy (RT) success in locally advanced or medically inoperable malignant pleural mesothelioma (MPM) patients. Recently, 18-fluorodeoxyglucose positron emission tomography (PET) has demonstrated significant improvements in diagnosis and accurate staging of MPM. However, role of additional PET data has not been studied in RT planning (RTP) of patients with inoperable MPM or in those who refuse surgery. Therefore, we planned to compare CT with co-registered PET-CT as the basis for delineating target volumes in these patients group.</p> <p>Methods</p> <p>Retrospectively, the CT and co-registered PET-CT data of 13 patients with histologically proven MPM were utilized to delineate target volumes separately. For each patient, target volumes (gross tumor volume [GTV], clinical target volume [CTV], and planning target volume [PTV]) were defined using the CT and PET-CT fusion data sets. The PTV was measured in two ways: PTV1 was CTV plus a 1-cm margin, and PTV2 was GTV plus a 1-cm margin. We analyzed differences in target volumes.</p> <p>Results</p> <p>In 12 of 13 patients, compared to CT-based delineation, PET-CT-based delineation resulted in a statistically significant decrease in the mean GTV, CTV, PTV1, and PTV2. In these 12 patients, mean GTV decreased by 47.1% ± 28.4%, mean CTV decreased by 38.7% ± 24.7%, mean PTV1 decreased by 31.1% ± 23.1%, and mean PTV2 decreased by 40.0% ± 24.0%. In 4 of 13 patients, hilar lymph nodes were identified by PET-CT that was not identified by CT alone, changing the nodal status of tumor staging in those patients.</p> <p>Conclusion</p> <p>This study demonstrated the usefulness of PET-CT-based target volume delineation in patients with MPM. Co-registration of PET and CT information reduces the likelihood of geographic misses, and additionally, significant reductions observed in target volumes may potentially allow escalation of RT dose beyond conventional limits potential clinical benefits in tumor control rates, which needs to be tested in future studies.</p

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Investigation of the genetic and epigenetic alterations in the promotor region of sFRP1 gene in chronic myeloid leukemia (CML) patients

Hematolojik malignansilerde Wnt Sinyal iletiminin deregülasyonu ilk olarak Kronik miyeloid lösemi'de(KML) tanımlanmıştır. Wnt sinyal iletiminin antagonistleri olan sFRP'ler (Secreted Frizzled related protein), Wnt proteinlerinin aktivitesini inhibe etme yeteneğine sahiptirler. sFRP genlerinin epigenetik sessizleşmesi, canonical Wnt sinyal iletiminin sürekli aktivasyonuna neden olmaktadır. Bu çalışmada 48 kronik faz KML hastasında sFRP1 geninin promotör bölgesindeki genetik ve epigenetik değişiklikler incelenmiştir. Yapılan iki yönlü DNA dizi analizinde, bu değişikliğin nükleotid 38, 39, 40. nükleotidlerde (CAG) çerçeve delesyonu olduğu gözlenmiştir. Bu üç nükleotidlik delesyon, kodon 13 ve 14'ü etkilemektedir ve ardarda gelen alanin rezidülerini kodlamaktadır. Oluşan yeni kodon yine alanin'dir. 48 kronik faz KML hastasının sFRP1 promotör metilasyon durumu incelendiğinde, bunların 1'inin tam metile, 41'inin metile olmayan, 6 'sının da hemimetile olduğu gösterildi. Her ne kadar sFRP1 promotör metilasyonu kronik faz KML'de sık gözlenmese de, hastalığın ilerleyişi ve terapiye dirençle ilişkili olduğu gözlenmiştir. 6 hemimetile hastanın 5'inde sadece parsiyel sitogenetik yanıt veya sitogenetik yanıt gözlenmezken, sFRP1 promotörü metile olmayan 41 hastanın tümünde majör veya tam sitogenetik yanıt izlenmiştir. Tam metile olan hastada, ek kromozomal anomalilerle birlikte sitogenetik ilerleme gözlenmiştir. sFRP1 promotör metilasyonu, hastalığın terapiye direnç gösteren ve genetik olarak stabil olmayan formunda terapiye dirençle ilişkilidir ve terapiye direnç gösteren hastalarda biyolojik farklılıklar yaratır. Ek olarak sFRP1 promotör metilasyonunun KML'de canonical Wnt sinyal iletiminin aktivasyonu için olası bir mekanizma olabileceği düşünülmektedir. The first description of deregulated Wnt signaling in a hematological malignancy was reported in chronic myeloid leukemia (CML). The Wnt signaling antagonists, secreted frizzled related proteins (sFRPs), are able to inhibit the activity of Wnt proteins. Epigenetic silencing of sFRP genes lead to constitutive activation of the canonical Wnt-signaling pathway. In this present study we investigated genetics and epigenetics alteration in promotor region of the sFRP1 gene in 48 chronic phase CML patients. Bi-directional sequencing show that the variation is an inframe deletion of nucleotides 38, 39 and 40 (CAG). This three-nucleotide deletion affects codons 13 and 14, and both encoding for consecutive alanin residues. The resulting just in-frame codon also encodes for alanin. When investigated methylation status of the sFRP1 promotor in 48 chronic phase CML patients show that it's fully methylated in 1, hemi-methylated in 6 and unmethylated in 41 patients. Albeit observed infrequently in chronic phase CML, sFRP1 promoter methylation correlates with therapy resistance and disease progression. Forty-one patients that were unmethylated at the sFRP1 promoter all achieved major or complete cytogenetic remissionæ while five of the six hemi-methylated patients have only achieved partial cytogenetic remission or no cytogenetic remission. The full-methylated patient has shown cytogenetic progression with additional chromosomal abnormalities. sFRP1 promoter methylation may indicate a genetically more unstable form of disease resistant to therapy and provide a key biological difference in therapy resistant patients. In addition to a possible mechanism for the observed activation of canonical Wnt signaling in CML

Volatiles and char combustion rates of demineralised lignite and wood blends

Today, much interest is given to the utilisation of materials of plant origin as substitutions of fossil fuels in meeting energy needs to reduce the level of atmospheric pollutant emissions and global warming threat, and emphasis has been placed on the co-combustion of coal and biomass. In this study, volatiles and char combustion behaviour of the fuel pellets composed from demineralised lignite and poplar wood sawdust, were investigated in a cylindrical wire mesh basket placed in a preheated tube furnace. The results have shown that ignition times of the pellets decreased with the burning temperature and shortened further due to demineralisation of lignite. Volatiles combustion rates of the samples did not correlate well with combustion times. However, they can be correlated with their respective proximate volatile matter contents. Char burnout times decreased with increasing combustion rates and correlated well with the respective proximate fixed carbon contents of the samples. Deviations were more considerable in the case of rate data.Co-combustion Lignite Poplar wood Volatiles combustion Char combustion