Cancer immunology and canine malignant melanoma: a comparative review

Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current “gold standard” treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics

Cohesin complex-associated holoprosencephaly

Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80–90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly

Cancer immunology and canine malignant melanoma: A comparative review

Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current “gold standard” treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics

Trial design: Blood pressure control and weight gain prevention in prehypertensive and hypertensive smokers: The treatment and prevention study

Ovaj završni rad bavi se motivacijom i nagrađivanjem zaposlenika u prodaji. Sama prodaja mijenjala se tijekom vremena i imala različita shvaćanja ljudi pa tako i mnoštvo definicija. Jedna od definicija označava prodaju kao međuljudski komunikacijski proces u kojem prodavač otkriva i zadovoljava potrebe kupca s ciljem ostvarenja uzajamnih dugoročnih koristi za obje strane. Kako bi se te koristi za obje strane ostvarile, potrebno je ustanoviti na koji način motivirati i nagraditi zaposlenika u prodaji da bi on uložio maskimalan napor u ostvarivanju toga cilja pomoću adekvatne kompenzacije za rad, odnosno nagrade. Najčešće se kompenzacije smatraju kao nagrade koje za rad u svom poduzeću dobivaju zaposlenici, a one mogu biti izražene u novcu, robi, bonovima, karticama potrošaća te drugim raznim oblicima nematerijalne i materijalne pomoći. Analizirajući dostupne radove kolega s istom ili sličnom tematikom, ustanovilo se kako motivacija i nagrade za rad različito djeluju na zaposlenike u prodaji. Dok neke motiviraju visina plaće i bonusi, druge motivira sigurnost zadržavanja posla i dobri odnosi s nadređenim. Sve navedeno još ovisi o raznim čimbenicima kao što su dob, spol, staž, stručna sprema, osobni doživljaj zaposlenika, sektor poslovanja, razne društvene i gospodarske prilike. Obzirom da se prodaja, kao i tržište, konstantno mijenja, menadžeri u prodaji i njihova poduzeća trebaju težiti pronalasku najefikasnijih rješenja za motivaciju i nagrađivanje zaposlenika, a sve s ciljem ostvarenja što većeg profita poduzeća.The subject of this thesis is motivation and compensation of sales employees. The sales itself underwent numerous changes during the cause of time, it had different understanding of people thus it had numerous definitions as well. One of the definitions refers to sales as an interpersonal communication process sin which the seller detects and meets the needs of the customer in order to achieve mutual long-term benefits for both parties. In order for these benefits to be mutually accomplished it is necessary to establish how to motivate and compensate the sales employee, through adequate work compensation i.e. reward, in order that he or she invests maximal effort in achieving of that goal. Most commonly compensations are considered as rewards that employees receive for their work in the company. The compensation can be in a form of money, goods, vouchers, consumer cards as well as in other forms of intangible and tangible benefits. Analysing available thesis of fellow colleagues with the same or similar topic, it was found that motivation and compensation for work have different effect on sales employees. While some are motivated by salary and bonuses, others are motivated by job security and good relations with their superiors. All afore mentioned also depends on additional factors such as age, gender ,work experience, level of education, personal experience of employees, business sector as well as various social and economic circumstances. Given that sales as well as market changes continuously, sales managers and their companies should strive to find the most effective solutions for motivation and compensation of employees thus aiming to maximise the profit of the company