Attenuation of skeletal muscle atrophy in cancer cachexia by d-myo-inositol 1,2,6-triphosphate

PURPOSE: To determine the effectiveness of the polyanionic, metal binding agent D-myo-inositol-1,2,6-triphosphate (alpha trinositol, AT), and its hexanoyl ester (HAT), in tissue wasting in cancer cachexia. METHODS: The anti-cachexic effect was evaluated in the MAC16 tumour model. RESULTS: Both AT and HAT attenuated the loss of body weight through an increase in the nonfat carcass mass due to an increase in protein synthesis and a decrease in protein degradation in skeletal muscle. The decrease in protein degradation was associated with a decrease in activity of the ubiquitin-proteasome proteolytic pathway and caspase-3 and -8. Protein synthesis was increased due to attenuation of the elevated autophosphorylation of double-stranded RNA-dependent protein kinase, and of eukaryotic initiation factor 2alpha together with hyperphosphorylation of eIF4E-binding protein 1 and decreased phosphorylation of eukaryotic elongation factor 2. In vitro, AT completely attenuated the protein degradation in murine myotubes induced by both proteolysis-inducing factor and angiotensin II. CONCLUSION: These results show that AT is a novel therapeutic agent with the potential to alleviate muscle wasting in cancer patients

Distribution-aware compressed full-text indexes

In this paper we address the problem of building a compressed self-index that, given a distribution for the pattern queries and a bound on the space occupancy, minimizes the expected query time within that index space bound. We solve this problem by exploiting a reduction to the problem of finding a minimum weight K-link path in a properly designed Directed Acyclic Graph. Interestingly enough, our solution can be used with any compressed index based on the Burrows-Wheeler transform. Our experiments compare this optimal strategy with several other known approaches, showing its effectiveness in practice

Protection against SARS-CoV-2 after Covid-19 vaccination and previous infection

Supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grants from the Medical Research Council.Background: The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters. Methods: We investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (≤10 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2. Results: Of 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 95% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously. Conclusions: Two doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection.Publisher PDFPeer reviewe

The impact of orthodontic treatment on choosing a career in dentistry

Introduction Many studies, globally, have aimed at elucidating reasons to choose a career in dentistry. The most common motives found are reasonable working hours and aspiration to help. The aim of this study was to explore whether eventual past personal experience of orthodontic treatment and particularly the interpersonal skills of the treating orthodontist are of significance in this respect. Materials and methods An electronic questionnaire, consisting of multiple choice and descriptive questions about dental history and experiences in dental care, was sent to dental and, as controls, psychology students within the same Faculty of Medicine, University of Helsinki, Finland. The answers between the two groups were compared and differences tested statistically. Results The questionnaire was answered by 143 (46.0%) dental students and 94 (17.6%) psychology students. Dental students, compared to psychology students, had more positive views of their dentition and dental treatment in general (p = 0.000). Amongst participants, 47.9% of dental students and 57.4% of psychology students had received orthodontic treatment. Of those, dental students had perceived their orthodontic treatment as less painful (p = 0.001) and less uncomfortable (p = 0.000) than psychology students. Moreover, dental students reported more often experiences of orthodontist taking into account their situation in life during treatment (p = 0.011) and gave more positive descriptions of the orthodontist's interpersonal skills (p = 0.031). Conclusions Dental students, compared to psychology students, had statistically significantly more positive personal experiences related to dentistry and orthodontics, supporting our hypothesis that positive experiences with orthodontic treatment likely increase the probability of choosing dentistry as the future career.Peer reviewe

Outcomes of High-Frequency Gastric Electric Stimulation for the Treatment of Severe, Medically Refractory Gastroparesis in Finland

Background and Aims: Severe, medically uncontrollable gastroparesis is a rare entity, which can be treated using a high-frequency gastric electric stimulator implanted surgically. Previous follow-ups have proven positive outcomes with gastric electric stimulator in patients with gastroparesis. The aim of this study was to evaluate the efficacy and safety of gastric electric stimulator in patients, in whom gastroparesis could not be controlled by conservative means in our country. Materials and Methods: This is a retrospective multi-center cohort comprising all patients who had been implanted gastric electric stimulator for severe, medically refractory gastroparesis during 2007-2015 in Finland. Results: Fourteen patients underwent implantation of gastric electrical stimulator without any postoperative complications. Laparoscopic approach was used in 13 patients (93%). Prior implantation, all patients needed frequent hospitalization for parenteral feeding, 13 had severe nausea, 11 had severe vomiting, 10 had notable weight loss, and 6 had frequent abdominal pain. After operation, none of the patients required parenteral feeding, 11 patients (79%) gained median of 5.1 kg in weight (P <0.01), and symptoms were relieved markedly in 8 and partially in 3 patients (79%). Of partial responders, two continued to experience occasional vomiting and one mild nausea. Five patients needed medication for gastroparesis after the operation. One patient did not get any relief of symptoms, but gained 6 kg in weight. No major late complications occurred. Conclusion: Gastric electrical stimulator seems to improve the nutritional status and give clear relief of the symptoms of severe, medically uncontrollable gastroparesis. Given the low number of operations, gastric electrical stimulator seems to be underused in Finland.Peer reviewe

Diagnosis, natural course and treatment outcomes of groove pancreatitis

Background: Groove pancreatitis (GP) is a rare form of chronic pancreatitis with limited data on its diagnostics and treatment outcomes. The aim of this study was to assess its diagnostics, natural course, and treatment options. Methods: The study is a retrospective population-based study from Southern Finland, including all patients with suspected GP between January 2005 and December 2015. Two certified gastrointestinal radiologists re-reviewed the imaging studies. The radiological re-review, clinical judgment, and final histopathology confirmed the GP diagnoses. Results: Out of 67 patients with possible GP, 39 patients were considered to have high radiological certainty of GP. Out of these 39, five patients had cancer instead. Thirty-three patients with confirmed GP formed the final study cohort. Patients with GP were mostly middle-aged (median 55 years) men. All had at least moderate alcohol consumption. No intervention was needed in 14 patients. In five-year follow-up all conservatively treated patients became asymptomatic, while 10 out of 16 patients undergoing at least one intervention were asymptomatic at five years. Conclusion: The radiological diagnosis of GP is difficult, and a low threshold for cancer suspicion should be kept. Symptoms of GP decrease with time and suggest conservative treatment as the first-line option.Peer reviewe

Oppilasarviointi ja monimateriaalisuus koulukäsityön haasteina:kirjallisuuskatsaus yhteisen käsityönopetuksen kontekstissa

Tiivistelmä. Tässä kandidaatintutkielmassa käsittelemme suomalaisen peruskoulun kontekstissa koulukäsityön oppilasarviointia, sekä uusimman opetussuunnitelmauudistuksen mukanaan tuomaa käsityönopetuksen monimateriaalisuutta, erityisesti monimateriaalisuusvaatimuksen tuomia haasteita. Yleisesti kaikkien taito- ja taideaineiden numeroarviointia on kritisoitu runsaasti. Ottaen huomioon, että mittauksissa on havaittu samantasoisen osaamisen tuottavan eri kouluissa hyvinkin erilaisia arvosanoja, on keskustelu hyvinkin ajankohtaista ja tarpeellista. Tasa-arvokeskusteluun paljon pohjautuva kaikille yhteinen monimateriaalinen käsityö on myös herättänyt paljon mielipiteitä niin puolesta, kuin vastaankin. Ilman ongelmia ja sopeutumista tämän tasoinen muutos ei toteudu hetkessä. Tutkimuskysymyksemme ovat, Miten oppilaita arvioidaan koulukäsityössä? Sekä mitä vaikeuksia teknisen työn ja tekstiilityön yhdistyminen monimateriaaliseksi käsityöksi on aiheuttanut opetustoiminnalle? Käsityöoppiaineen arviointia ohjaillaan muiden oppiaineiden tapaan lainsäädännöllä, sekä valtakunnalliselta tasolta kunta- ja koulukohtaisiksi tarkentuvilla opetussuunnitelmilla. Kuitenkin opettajalla on paljon vapauksia opetuksen toteuttamisen suhteen, sillä erityisesti valtakunnallisen opetussuunnitelman tasolla kriteerit ja vaatimukset ovat melko laajoja. Opetushallitus on helpottanut opettajien toimintaa laajentamalla päättöarviokriteereitä kuvailemaan sanallisesti arvosanoihin 5, 7, 8 ja 9 vaadittavaa osaamista. Myös yhteiskunnan muuttuminen aiempaa tasa-arvoisemmaksi on kannustanut edistämään myös perinteisesti hyvin sukupuolittuneen käsityöoppiaineen tasa-arvioisuutta. Tyttöjen ja poikien käsitöiksi alun perin jaoteltu oppiaine on muuttunut kaikille yhteiseksi, monimateriaaliseksi käsityönopetukseksi. Muutos on kuitenkin aiheuttanut ongelmia erityisesti vähäisten resurssien, erillisiksi rakennettujen oppimisympäristöjen, sekä lisääntyneiden osaamisvaatimusten takia

Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocyte cells through the classical EPO receptor

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in non-hematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP)). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects