A Screening Method for the ALK Fusion Gene in NSCLC

Lung cancer research has recently made significant progress in understanding the molecular pathogenesis of lung cancer and in developing treatments for it. Such achievements are directly utilized in clinical practice. Indeed, the echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (ALK) fusion gene was first described in non-small cell lung cancer in 2007, and a molecularly targeted drug against the fusion was approved in 2011. However, lung cancer with the ALK fusion constitutes only a small fraction of lung cancers; therefore, efficient patient selection is crucial for successful treatment using the ALK inhibitor. Currently, RT-PCR, fluorescent in situ hybridization (FISH), and immunohistochemistry are commonly used to detect the ALK fusion. Although FISH is currently the gold standard technique, there are no perfect methods for detecting these genetic alterations. In this article, we discuss the advantages and disadvantages of each method and the possible criteria for selecting patients who are more likely to have the ALK fusion. If we can successfully screen patients, then ALK inhibitor treatment will be the best example of personalized therapy in terms of selecting patients with an uncommon genotype from a larger group with the same tumor phenotype. In other words, the personalized therapy may offer a new challenge for current clinical oncology

Ophthalmic Features in Prader-Willi Syndrome Patients with Type-2 Diabetes Mellitus

Purpose：To investigate and compare features of diabetic retinopathy（DR）in patients with Prader-Willi Syndrome（PWS）and those without PWS.Methods：Overall, 33 PWS patients with type-2 diabetes mellitus（T2DM）secondary to PWS（65 eyes） and 55 age-matched patients with T2DM（109 eyes）without congenital heredity diseases were reviewed. Medical records of 65 eyes with PWS（PWS group：mean age 24.7±5.9 years）and 109 eyes without PWS （control group：mean age 22.9±6.2 years）were acquired and compared from January 2000 to November 2018. Best-corrected visual acuity（BCVA）was determined and DR scores were assigned.Results：BCVA was significantly low in PWS group compared with the controls（P＜0.001）. Pseudophakia was frequently observed in patients in the PWS group（P＝0.024）. No significant differences were found with respect to cataract（P＝0.065）and DR score（P＝0.77）between patients in the PWS and control groups. Investigations into the possible causes of the low BCVA in the PWS group found no significant difference regarding strabismus（P＝0.065）. However, significant differences were found between both groups with respect to amblyopia（P＜0.01）. Visual acuity examinations were incomplete in some patients with PWS because of their inability to concentrate（P＜0.01）.Conclusions：There was no correlation between DR progression and PWS. Lower BCVA in PWS patients was likely owing to amblyopia and incomplete visual acuity examination owing to inability of patients with PWS to concentrate

Muisti ja Arki : Ajankohtaista tietoa muistisairauksista, niiden ennaltaehkäisemisestä sekä arjesta muistisairauden kanssa

Suomen väestön ikärakenne muuttuu nopeasti lähivuosikymmeninä. Tilastokeskuksen ennusteiden mukaan yli 75-vuotiaiden määrä kaksinkertaistuisi vuoteen 2030 mennessä, joten muistisairauksien esiintyvyys tulee myös lisääntymään ikääntyvien määrän kasvaessa. Opinnäytetyömme idea sai alkunsa SenioriKaste-hankkeelta, joka toivoi ensitietopäivän järjestämistä Keski-Pohjanmaan alueella muistisairauksiin sairastuneille sekä heidän läheisilleen. Opinnäytetyömme tarkoituksena oli järjestää muistisairauksia käsittelevä tilaisuus muistisairauteen sairastuneille sekä heidän läheisilleen. Tilaisuus oli myös avoin kaikille asiasta kiinnostuneille. Opinnäytetyömme tavoitteena oli välittää muistisairauteen sairastuneille ja heidän läheisilleen ajankohtaista tietoa muistisairauksista sekä keinoista, joiden avulla kotona pärjääminen onnistuu mahdollisimman pitkään. Kartoitimme yhteistyökumppaneidemme kautta aiheen tärkeyttä ja tarvetta. Heidän asiakkailtaan saadun palautteen perusteella varmistuimme tilaisuuden järjestämisen tärkeydestä ja tiedon tarpeellisuudesta. Opinnäytetyömme toteutui toiminnallisena projektityönä yhteistyössä toimeksiantajan SenioriKaste-hankkeen kanssa Kokkolassa 4.6.2015. Tilaisuudessa luennoitiin muistisairauksien ennaltaehkäisemisestä, yleisimmistä muistisairauksista, muistisairauksien varhaisesta tunnistamisesta sekä niiden tuomista haasteista ja vaikutuksista ihmisen jokapäiväiseen elämään. Tilaisuuteen osallistui yhteensä 140 henkilöä. Osallistujilta kerättiin kirjallinen palaute. Palautekyselyistä tehtiin yhteenveto ja kehittämisehdotukset kirjattiin myös opinnäytetyöhön. Tilaisuus vastasi yleisesti osallistujien odotuksia kiitettävästi. Projekti toteutettiin parityöskentelynä, jossa onnistuimme kiitettävästi.The age structure of Finnish population is changing rapidly within the next few decades. Statistics prognosis is that the number of over 75 years old people will be doubled by 2030, so the occurrence of memory disorders will increase with aging people. The idea for this study got its start from Senior Initiation project that wished a public lecture to be organized in Central Ostrobothnia for patients with memory disorder and their families. The purpose of our study was to organize a memory disorder event for the aforementioned groups. The occasion was open for anyone who was interested in it. The aim of this study was to provide current information to memory disorder patients and their loved ones about memory disorders and ways to cope with it at home as long as possible. Through our co-operation partners we surveyed the importance and need of the topic. Based on the feedback from their clients we were convinced of the importance of the event and the need for information. Our thesis was completed as a functional project work together with our client Senior Initiation project in Kokkola 4th of June 2015. The prevention of memory disorders, most common memory disorders, their early recognition and the challenges and effects they bring to people’s everyday lives were discussed during this event. The total of 140 people took part in the event. A written feedback was collected from all participants. A summary was made from the feedback survey, and all development proposals were registered also in this thesis. The event corresponded in general to the participants’ expectations very well. The project was implemented as pair work, in which we succeeded commendably

The genome sequence of pepper vein yellows virus (family Luteoviridae, genus Polerovirus)

The complete genome of pepper vein yellows virus (PeVYV) was sequenced using random amplification of RNA samples isolated from vector insects (Aphis gossypii) that had been given access to PeVYV-infected plants. The PeVYV genome consisted of 6244 nucleotides and had a genomic organization characteristic of members of the genus Polerovirus. PeVYV had highest amino acid sequence identities in ORF0 to ORF3 (75.9 - 91.9%) with tobacco vein distorting polerovirus, with which it was only 25.1% identical in ORF5. These sequence comparisons and previously studied biological properties indicate that PeVYV is a distinctly different virus and belongs to a new species of the genus Polerovirus

Biliary reconstruction with right hepatic lobectomy due to delayed management of laparoscopic bile duct injuries: a case report.

We report a case requiring biliary reconstruction with right hepatic lobectomy due to biliary strictures caused by continuous cholangitis after laparoscopic bile duct injury. The patient, a 55-year-old woman, underwent laparoscopic cholecystectomy for cholelithiasis at another hospital. Although a bile leakage from the intraabdominal drain was observed several days after the operation, the patient was not given adequate treatment to stop the leakage. Two months after the initial laparoscopic cholecystectomy, she was referred to our hospital. Endoscopic retrograde cholangiopancreatography (ERCP) showed complete obstruction of the common hepatic duct, which was caused by clipping during laparoscopic cholecystectomy. Cholangiography from percutaneous transhepatic biliary drainage (PTBD) catheters revealed that sections of the secondary branches of the right intrahepatic bile duct had become constricted due to persistent cholangitis. Fortunately, the left hepatic duct was judged to be normal by imaging. Therefore, we elected to perform a right hepatic lobectomy and left hepaticojejunostomy, because we felt that performing a hepaticojejunostomy without hepatic resection would put the patient at risk of continuing to suffer from cholangitis. The patient was discharged on the 55 th postoperative day, and, 5 years after reconstructive surgery, is healthy and has remained free from biliary strictures in the remnant liver. Appropriate decision-making is essential in the treatment of biliary injury after laparoscopic cholecystectomy. Surgeons should not hesitate to perform biliary reconstruction with hepatic resection to reduce the risk of cholangitis or biliary strictures of the remnant liver. More importantly, preoperative clear imaging of the biliary tree and suitable management of any biliary injury which might occur are necessary to avoid having to perform reconstructive surgery.</p

Evaluation and selection of potent fluorescent immunosensors by combining fluorescent peptide and nanobodies displayed on yeast surface

Quenchbody (Q-body) is a quench-based fluorescent immunosensor labeled with fluorescent dye(s) near the antigen-binding site of an antibody. Q-bodies can detect a range of target molecules rapidly and directly. However, because Q-bodies show different antigen responses depending on the antibody used, time-consuming optimization of the Q-body structure is often necessary, and a high-throughput screening method for discriminating and selecting good Q-bodies is required. Here, we aimed to develop a molecular display method of nanobody-based “mini Q-bodies” by combining yeast surface display and coiled-coil forming E4/K4 peptide-based fluorescence labeling. As a result, the yeast-displayed mini Q-body recognizing the anti-cancer agent methotrexate (MTX) showed significant quenching and MTX-dependent dequenching on cells. To demonstrate the applicability of the developed method to select highly responsive mini Q-bodies, a small nanobody library consisting of 30 variants that recognize human serum albumin was used as a model. The best variant, showing a 2.4-fold signal increase, was obtained through selection by flow cytometry. Furthermore, the same nanobody prepared from Escherichia coli also worked as a mini Q-body after dye labeling. The described approach will be applied to quickly obtain well-behaved Q-bodies and other fluorescent biosensors for various targets through directed evolutionary approaches