It isn't over ‘till it’s over: A continuing concern of the SARS-CoV-2 variants, and miRNAs targeting the S protein as a probable absolute cure

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak which still continues to affect the general population, has mutated day by day and new variants have emerged. More than 40 variants, usually caused by mutations in the spike (S) protein, have been recorded. Observation of S protein mutations in the development of t herapeutic agents will increase success rates. As we identify the three-dimensional (3D) conformation of viruses, it is more and more possible to work on models for understanding molecular interactions. Development of agents for arrays and 3D sequencing of proteins paves the way for potential therapeutic studies against variants. MicroRNAs (miRNAs) seemingly act as a potentially important group of biomolecules in combating uncontrolled cytokine release. Besides antiviral response, miRNAs promise to be  powerful therapeutic agents against infections. Studies have shown that miRNAs are able to inhibit the genome directly by miRNA-based treatments as they are sprecific to the SARS-CoV-2 genome. In order to expose this potential, in silico studies before continuing with lab studies are helpful. In our bioinformatics analysis, we proposed to compare the S protein similarities of Delta and Omicron, two of the most common variants, and to detect miRNAs targeting the S protein. The S proteins and coding sequences were compared between the two variants, and differences were determined. Within our analysis, 105 and 109 miRNAs for the Delta and Omicron variants, respectively, were detected. We believe that our study will be a potential guide for deciding on the miRNAs that may most likely have an effect on the management of the infection caused by both variants

Türkiye akademik CAR-T hücre (ISIKOK-19) klinik çalışması ön raporu: Ürün karakterizasyonu ve klinik uygulama sonuçları

Objective: Chimeric antigen receptor T (CAR-T) cell therapies have already made an impact on the treatment of B-cell malignancies. Although CAR-T cell therapies are promising, there are concerns about commercial products regarding their affordability and sustainability. In this preliminary study, the results of the first production and clinical data of an academic CAR-T cell (ISIKOK-19) trial in Turkey are presented. Materials and Methods: A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy for patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. The production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusions are presented in this study. Results: Nine patients were enrolled in the trial [5 with acute lymphoblastic leukemia (ALL) and 4 with non-Hodgkin lymphoma (NHL)], but only 7 patients could receive treatment. Two of the 3 participating ALL patients and 3 of the 4 NHL patients had complete/ partial response (overall response rate: 72%). Four patients (57%) had CAR-T-related toxicities (cytokine release syndrome, CAR-T-related encephalopathy syndrome, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up. Conclusion: Production efficacy and fulfillment of the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles were also acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19+ tumors. However, the findings of this study need to be supported by the currently ongoing ISIKOK-19 clinical trial.Amaç: Kimerik antijen reseptör T (CAR-T) hücre uygulamaları B-hücreli malignitelerin tedavisinde etkili olmaktadır. CAR-T hücre uygulamalarının sonuçları umut vaadedici olsa da, ticari CAR-T ürünlerinin yükek maliyetleri nedeniyle ulaşılabilirlik açısından ciddi sorunlar yaşanmaktadır. Bu ön raporda, Türkiye’deki ilk akademik CAR-T hücre çalışmasının üretim ve klinik uygulama sonuçları sunulmuştur. Gereç ve Yöntemler: Relaps refrakter CD 19+ hematolojik maligniteli hastalarda ISIKOK-19 T-hücre tedavisinin güvenliği ve etkinliğini değerlendirmek amacıyla yürütülen klinik çalışmaya (NCT04206943) Ekim 2019-Temmuz 2021 tarihleri arasındaki hastalar dahil edilmiştir. Bu raporda ilk 8 hastanın üretim bilgileriyle, ISIKOK-19 hücre infüzyonu yapılan 7 hastanın klinik sonuçları sunulmuştur. Bulgular: Çalışmaya toplam 9 hasta dahil edilmiştir (5 akut lenfoblastik lösemi [ALL] ve 4 non-hodgkin lenfoma [NHL]), ancak sadece 7 hastaya hücre infüzyonu yapılabilmiştir. Hücre infüzyonu alan 3 ALL hastasından 2’sinde ve 4 NHL hastasının 3’ünde tam/kısmi cevap gözlenmiştir (toplam yanıt oranı %72). Dört hastada (%57) CAR-T ilişkili toksisite (sitokin salınım sendromu, immün efektör hücre ilişkili nörotoksisite sendromu ve pansitopeni) tespit edilmiştir. İki hastada ise CAR-T hücre uygulaması sonrası cevapsızlık ve progresif hastalık izlenmiştir. Kısmi cevap veren hastalardan 2’sinde de takip sırasında progresif hastalık tespit edilmiştir. Sonuç: Akademik CAR-T üretimimiz, üretim etkinliği ve kalite kontrol kriterlerinin tam olarak karşılanması açısından tatmin edici sonuçlara sahiptir. Çalışmaya dahil edilen hastaların tedavi yükü hesaba katıldığında tedaviye cevap oranı ve toksisite profili açısından da sonuçlar kabul edilebilir düzeydedir. Bu sonuçlarla, ISIKOK-19 hücrelerinin güvenli, ekonomik ve etkili bir tedavi seçeneği olduğu düşünülebilir. Ancak bu ön sonuçların halen devam eden ISIKOK-19 klinik çalışmasıyla desteklenmesi beklenmektedir

The insidence of the congenital anomalies in pediatric oncology patients

Çocukluk çağı kanserlerinin birçoğunun etyolojisi net açıklanamamıştır. Son çalışmalar, anomalilerin genetik ve çevresel faktörlerin de etkisi ile kanser gelişiminde rol alabileceğini göstermiştir. Bu çalışmanın amacı, maligniteler ve konjenital anomaliler arasındaki ilişkinin araştırılması ve çeşitli kanserlere en sık eşlik eden anomalilerin belirlenmesidir. Çalışmamızda Uludağ Üniversitesi Tıp Fakültesi Çocuk Onkoloji Bilim Dalı'nda takipli, solid tümör veya lenfoması olan 506 hasta incelenmiştir. Hastalardaki malignite dağılımına bakıldığında 135 (%27) hasta sayısı ile lenfomalar birinci sıradadır. Bunu 65 (%13) hasta ile santral sinir sistemi tümörleri ve 63 (%12) hasta ile germ hücreli tümörler takip etmektedir. Hastaların %33.5'inde (n=170) anomali olduğu görülmüştür. Bu 170 hastada, 241 farklı anomali tanımlanmıştır. Bu anomalilerin %30.7'sinin göz, kulak, yüz, boyun anomalileri, %18.25'inin kardiyovasküler sistem anomalileri, %10.78'inin ürogenital sistem anomalileri, %9.12'sinin SSS anomalileri, %7.05'inin kas iskelet sistemi anomalileri, %6.27'sinin sindirim sistemi anomalileri, %2.48'inin solunum sistemi anomalileri, %15.35'inin ise diğer anomaliler grubunun anomalileri olduğu görülmüştür. Hastaların demografik özelliklerine bakıldığında; hastaların %44.6'sı (n=226) kız, %55.4'ü (n=280) erkektir. Hastaların ortalama yaşı 7.34±5.46 yıldır. Doğumdaki ortalama anne yaşı 26.83±5.17, ortalama baba yaşı ise 30.02±5.41'tir. Soygeçmişlerine bakıldığında %20.4'ünde (n=103) annede düşük veya ölü doğum öyküsü olduğu, %28.1'inde (n=142) akrabalarında kanser öyküsü olduğu ve %14.2'sinin (n=72) anne ve babası arasında akrabalık olduğu görülmüştür. Anomalisi olan hastaların %25'inin doğumdaki baba yaşının 35 yaş ve üzeri olduğu görülmüştür (p:0.004). Malignitelerde anomali görülme sıklığı incelendiğinde; SSS tümörü olan hastalarda anomali görülme sıklığı %61.5 (n=40) olarak saptanmıştır (p<0.001). Böbrek tümörlü hastaların %32.7'sinde, sarkomlu hastaların %32.2'sinde, nöroblastomlu hastaların %31.6'sında ve lenfomalı hastaların %27.4'ünde anomali olduğu görülmüştür. SSS tümörü olan hastaların %32.3'ünde (n=21) göz, kulak, yüz, boyun anomalisi saptanmış ve diğer malignite gruplarına göre istatistiki olarak anlamlı oranda sık bulunmuştur (p<0.001). SSS anomalisi olan hastaların %36.3'ünde SSS tümörü mevcuttur ve bu gruptaki en sık görülen malignite grubudur. Göz, kulak, yüz, boyun anomalisi olan 58 hastanın %28.3'ünde (n=21) de SSS tümörü olduğu görülmüştür. Ekokardiyografisi olan hastaların %20.5'sinde (n=44) kardiyak anomali tespit edilmiştir. Malignite grupları arasında kardiyovasküler sistem anomalisi görülme sıklığı açısından fark görülmemiştir. Germ hücreli tümörü olan hastaların ekokardiyografisi olanlar içerinde %35.7'sinde, böbrek tümörü olanların %31'inde, yumuşak doku sarkomu olanların %26.7'sinde kardiyovasküler anomali saptanmıştır. Sonuç olarak; anomaliler ve maligniteler arasında bir ilişki olduğu açıktır. Kanser gelişiminde ve özellikle embriyolojik gelişim evreleri sırasında gelişen konjenital anomalilerde rol alan genlerle ilgili yapılacak olan ileri çalışmalar değerli bilgiler sağlayabilir. Bu alanda yapılacak çok daha geniş kapsamlı çalışmalara ihtiyaç vardır.The etiology of a large number of childhood cancers is not clear. Recent studies have shown that anomalies may play a role in the development of cancer by the effects of genetic and environmental factors. The aim of this study was to investigate the relationship between malignancies and congenital anomalies and to identify the most common anomalies associated with various cancers. In our study, 506 patients with solid tumors or lymphoma who were followed up at Uludag University Faculty of Medicine, Department of Pediatric Oncology were examined. The distribution of malignancies among the patients revealed that 135 (27%) patients had lymphoma, the leading malignancy in this category, followed by 65 (13%) patients with central nervous system (CNS) tumors and 60 (12%) with neuroblastoma. It was found that 33.5% (n = 170) of the patients had anomalies. In these 170 patients, 241 different anomalies were identified. Distribution of these anomalies is 30.7% eye, ear, face, neck anomalies and 18.25% cardiovascular system anomalies, 10.8% urogenital system anomalies, 9.12% CNS anomalies, 7.05% musculoskeletal system anomalies, 6.27% digestive system anomalies, 2.48% respiratory system anomalies and 15.35% other anomalies. Demographic characteristics of the patients are examined; 44.6% of the patients (n = 226) were female and 55.4% (n = 280) were male. The mean age of the patients was 7.34 ± 5.46 years. Mean maternal age at birth was 26.83 ± 5.17, and mean father age was 30.02 ± 5.41. When the patient's family history is examined, It was found that 20.4% (n = 103) had a history of low or stillbirth in the mother, 28.1% (n = 142) had cancer stories in their relatives and 14.2% (n = 72) had consanguineous marriage. It was observed that 25% of patients with anomalies had a father of age 35 years and older at birth. This result was statistically significant when compared to the group without anomalies (p:0.004). The frequency of anomalies in malignant groups were examined; the incidence of anomalies in patients with CNS tumors was 61.5% (n = 40) (p <0.001). It was found that, in 32.7% of renal tumor patients, in 32.2% of patients with sarcoma, in 31.6% of neuroblastoma and in 27.4% of lymphoma patients had an anomaly. Eye, ear, face and neck anomalies were found in 32.3% (n = 21) of patients with CNS tumors and statistically significant frequency was found to be statistically significant compared to other malignancy groups (p <0.001). CNS tumors are present in 36.3% of patients with CNS anomalies and this group is the most common malignancy group. Of the 58 patients with eye, ear, face, and neck anomalies, 36.2% (n = 21) had CNS tumors. Cardiac anomaly was detected in 20.5% (n = 44) who examined with echocardiography. There was no difference in the incidence of cardiovascular system anomalies between malignant groups; but the incidence of cardiovascular system anomalies in malignancy groups is significantly higher. Cardiovascular abnormalities were detected in 35.7% of patients with germ cell tumors, 31% of those with renal tumors, and 26.7% of those with soft tissue sarcomas. Consequently; it is clear that there is an association between anomalies and malignancies. Further studies on cancer development and genes involved in congenital anomalies that occur especially during embryological developmental stages may provide valuable information regarding this subject. There is a need for much more extensive work to be done on this topic. We suppose that our study will contribute to the malignancy-anomaly relationship to be investigated later on

Intuitionistic smooth topology

Tez (Yüksek lisans) -- Giresun Üniversitesi. Kaynakça var.v , 46 s. ; 28 cm.Demirbaş: 0063574

Effects of Acetylcholinesterase Inhibitors on Balance and Gait Functions and Orthostatic Hypotension in Elderly Patients With Alzheimer Disease

Objective: The present study was designed to evaluate the effect of acetylcholinesterase inhibitor (AchEI) therapy on balance, gait, and orthostatic hypotension (OH) in elderly patients with Alzheimer's disease (AD). Methods: A total of 102 elderly patients with AD have been recently diagnosed and were treated with AchEI and underwent comprehensive geriatric assessment at baseline and at the end of the sixth month. Results: Timed Up and Go test and Tinetti Performance-Oriented Mobility Assessment values and the prevalence of OH were not different at the end of the sixth month versus baseline (P >.05). However, it was determined that changes in balance were better in the patients who showed cognitive improvement at the end of the sixth month (P <.05). Conclusion: Curative effects of AchEIs, which are used in the treatment of AD, on cognitive performance are reflected also in balance functions. Moreover, it was observed that these drugs do not increase the prevalence of OH

The effects of sitagliptin, a DPP-4 inhibitor, on cognitive functions in elderly diabetic patients with or without Alzheimer's disease

Aims: The present study aimed to evaluate effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4I), on cognitive functions in elderly diabetic patients with and without cognitive impairment

Triple test, a diagnostic observation, can detect cognitive impairment in older adults

BackgroundA simple, quick, and efficient screening tool for detecting mild cognitive impairment (MCI) and Alzheimer's disease (AD) is essential, especially in the primary care setting. In this study, we examined the neuropsychological profiles of elderly patients and aimed to assess the diagnostic value of the triple test, comprised of the attended alone sign (AAS), head-turning sign, and applause sign (AS), for detecting MCI and AD